- Signal amplification and transduction by photo-activated catalysis
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A simple flavin-based catalytic system is able to transform light into chemical output with amplified response utilizing a Cu(i)-catalyzed cycloaddition reaction. The Royal Society of Chemistry.
- Ritter, Stefan C.,Koenig, Burkhard
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- Site-directed attachment of photoexcitable spin labels for light-induced pulsed dipolar spectroscopy
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Photoexcited triplet states are gaining popularity as spin labels in pulsed electron paramagnetic resonance (EPR) spectroscopy. Here, we demonstrate that the fluorophores Eosin Y, Rose Bengal and Atto Thio12 are suitable markers for distance determination
- Williams, Lara,Tischlik, Sonja,Scherer, Andreas,Fischer, J?rg Wolfram Anselm,Drescher, Malte
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- Anthranilic Acid as a Versatile Fluorescent Tag and Linker for Functional Glycomics
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The advancement of glycoscience is critically dependent on the access to a large number of glycans for their functional study. Naturally occurring glycans are considered a viable source for diverse and biologically relevant glycan libraries. A mixture of free reducing glycans released from natural sources can be fluorescently tagged and separated by chromatography to produce a natural glycan library. Anthranilic acid (AA) has been widely used to fluorescently tag reducing glycans for HPLC or LC/MS analysis. However, AA conjugated glycans are not efficiently immobilized on microarray slides due to the lack of a primary alkylamine functional group. In this study, we have developed simple and efficient chemistry for bioconjugation and further functionalization of glycan-AA conjugates. This new approach enables quick preparation of glycan microarrays and neoglycoproteins from glycan-AA conjugates, which can be separated by weak anion exchange (WAX) and C18 reversed-phase HPLC.
- Zhu, Yuyang,Liu, Xueyun,Zhang, Ying,Wang, Zhongfu,Lasanajak, Yi,Song, Xuezheng
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- Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase
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Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits ~200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.
- Sugawara, Akihiro,Maita, Nobuo,Gouda, Hiroaki,Yamamoto, Tsuyoshi,Hirose, Tomoyasu,Kimura, Saori,Saito, Yoshifumi,Nakano, Hayato,Kasai, Takako,Nakano, Hirofumi,Shiomi, Kazuro,Hirono, Shuichi,Watanabe, Takeshi,Taniguchi, Hisaaki,Omura, Satoshi,Sunazuka, Toshiaki
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- Novel thermoresponsive polymers tunable by pH
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Thermoresponsive polymers that are pH tunable were successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide and alkynes (click chemistry). ATRP was employed to synthesize poly(2-hydroxyethyl methacrylate) (PHEMA), followed by introduction of alkyne groups using pentynoic acid, leading to PHEMA-alkyne. 2-Azidoethylamine, 2-azido-N,N-dimethylethylamine, and 2-azido-N,N-diethylethylamine were added to the PHEMA-alkyne backbone via click chemistry. Molecular weight, molecular weight distribution, and click reaction efficiency were determined by gel permeation chromatography (GPC) and 1H NMR spectroscopy. The average molecular weight (Mn) of the resulting polymers ranged from 5.6 ×104 to 7.0 ×104 depending on the molecular architecture. The molecular weight distribution was low (Mn/Mn = 1.25-1.35). The transmission spectra of the 0.1 wt % aqueous solutions of the resulting polymers with different pH values at 650 nm were measured as a function of temperature. Results showed that the lower critical solution temperature (LCST) could be dramatically affected by solution pH. To give additional evidence for pH-responsive thermal transition, in-situ temperature-dependent 1H NMR measurements in deuterated water (0.01 wt %) were conducted. The LCST values measured by in-situ 1H NMR correlated well with those determined by turbidimetry.
- Jung, Seo-Hyun,Song, Hye-Young,Lee, Youngil,Jeong, Han Mo,Lee, Hyung-Il
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- Interface immobilization chemistry of cRGD-based peptides regulates integrin mediated cell adhesion
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The interaction of specific surface receptors of the integrin family with different extracellular matrix-based ligands is of utmost importance for the cellular adhesion process. A ligand consists of an integrin-binding group, here cyclic RGDfX, a spacer molecule that lifts the integrin-binding group from the surface and a surface anchoring group. c(-RGDfX-) peptides are bound to gold nanoparticle structured surfaces via polyproline, polyethylene glycol or aminohexanoic acid containing spacers of different lengths. Although keeping the integrin-binding c(-RGDfX-) peptides constant for all compounds, changes of the ligand's spacer chemistry and length reveal significant differences in cell adhesion activation and focal adhesion formation. Polyproline-based peptides demonstrate improved cell adhesion kinetics and focal adhesion formation compared with common aminohexanoic acid or polyethylene glycol spacers. Binding activity can additionally be improved by applying ligands with two head groups, inducing a multimeric effect. This study gives insights into spacer-based differences in integrin-driven cell adhesion processes and remarkably highlights the polyproline-based spacers as suitable ligand-presenting templates for surface functionalization. Self-organized spatial positioning of cRGD patches on glass via a gold nanopattern as a biomimetic approach to engineer cellular environments. Regulation of integrin-mediated cellular responses is achieved by tuning the length and chemical nature of the cRGD-presenting molecule. Fibroblasts exhibit higher affinity towards surfaces coated with cRGD containing a polyproline spacer compared with alkane- and polyethylene glycol-based spacers.
- Pallarola, Diego,Bochen, Alexander,Boehm, Heike,Rechenmacher, Florian,Sobahi, Tariq R.,Spatz, Joachim P.,Kessler, Horst
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- Biological evaluation of avidin-based tumor pretargeting with DOTA-Triazole-Biotin constructed via versatile Cu(I) catalyzed click chemistry
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Background: The biotin-avidin interaction remains a gold standard for the two-step pretargeting approach to image tumor sites. We aim to develop two-step pretargeting systems utilizing 99mTc labeled biotin functionalized macrocyclic chelating agents synthesized using the highly efficient Cu(I) catalyzed azide-alkyne cycloaddition for potential radioimaging applications. Methods: A facile synthesis of DOTA-Triazole-Biotin, radiocomplexation with 99mTc and the pretargeting protocol is described. The synthesis features Cu(I) catalyzed click conjugation between biotinylated azide and propynyl functionalized DO3A. 99mTc radiolabeling was performed to detect the accumulation of avidin as the pretargeting agent. Cytotoxicity was determined using the trypan blue exclusion assay, macrocolony, and MTT assay. Cell uptake studies were performed using radiolabeled DOTA-Triazole-Biotin and compared with avidin treated cells for 2 h. Tumor imaging was performed in U-87MG cell line implanted tumor bearing nude mice and uptake of the radiotracer was estimated. Results: All compounds have been successfully characterized by NMR and MS spectroscopy. More than 96% radiolabeling efficiency was obtained and the radioconjugate exhibited sufficient stability under physiological conditions. Conclusion: To summarize, a new candidate for avidin based two-step pretargeting of tumors has been synthesized and evaluated for potential imaging and diagnostic applications. The chelate possesses high stability under physiological conditions, exhibits effective interaction with its avidin target, and low nonspecific retention in vivo.
- Uppal, Jasleen Kaur,Varshney, Raunak,Hazari, Puja Panwar,Chuttani, Krishna,Kaushik, Narender Kumar,Mishra, Anil Kumar
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- Amino-functionalized single-chain bolalipids: Synthesis and aggregation behavior of new basic building blocks
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Herein, we report the synthesis of two novel, amino-functionalized single-chain bolalipids and, based on those, a general synthetic approach for the insertion of various carboxylic acids into the bolalipid headgroups, e.g. α-lipoic acid for one-dimensional fixation of gold nanoparticles, sorbic acid for polymerization experiments, or lysine for the use in gene delivery systems. The temperature- and pH-dependent self-assembly of amino-functionalized bolalipids into nanofibers and micelles was investigated by differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Rheological measurements were used to describe the macroscopic behavior of the formed temperature switchable hydrogels that can be fine-tuned for drug delivery applications. We showed that the viscoelastic properties of the hydrogel strongly depend on ionic interactions between bolalipid headgroups as well as on the ability to form hydrogen bonds.
- Drescher, Simon,Graf, Gesche,Hause, Gerd,Dobner, Bodo,Meister, Annette
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- Enhanced osteogenic differentiation of MC3T3-E1 on rhBMP-2-immobilized titanium via click reaction
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In the present study, we report about the efficacy of titanium surface-immobilized with bone morphogenetic protein-2 (BMP-2) via click reaction on enhanced osteogenic differentiation of MC3T3-E1 cells. The surface was characterized by static contact angles and XPS measurements, which indicated that pristine titanium (Ti-1) was successfully surface-modified via click chemistry (aminated titanium, Ti-4). By quantitative analysis of heparin immobilized on aminated titanium (Ti-4), we found that the Ti-4 can be used as a good candidate to immobilize biomolecules such as heparin. BMP-2 from titanium immobilized with BMP-2 (Ti-6) was released for a period of 28 days in a sustained manner. The highest proliferation rate of MC3T3-E1 cells was observed on Ti-6. Through in vitro tests including alkaline phosphatase (ALP) activity, calcium deposition and real-time polymerase chain reaction (real-time PCR), we found that Ti-6 can be used as a good implant to enhance the osteogenic differentiation of MC3T3-E1 cells.
- Kim, Eun-Cheol,Kim, Tae-Hee,Jung, Jae-Hoon,Hong, Sung Ok,Lee, Deok-Won
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- A general method for functionalisation of microgel particles with primary amines using click chemistry
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In this study we introduce a general method for functionalising microgel particles with primary amine groups using a one-step copper catalysed azide-alkyne cycloaddition (CuAAC) reaction. Three different families of microgels containing copolymerised propargyl acrylate (PA) were prepared and then reacted with 2-azido-1-ethylamine (AEA) using CuAAC. The microgels contained poly(ethyl acrylate) (PEA), poly(2-vinylpyridine) (PVP) or poly(N-isopropylacrylamide) (PNP). The functionalisation of the microgels containing PA (i.e., PX-PA) by AEA to give primary amine functionalised particles (PX-PA-AEA) was assessed by elemental analysis and FTIR. The reaction of AEA with PA was quantitative for each of the PX-PA-AEA microgels (X = EA, VP and NP). The PX-PA-AEA systems generally showed larger pH-triggered swelling and zeta potentials than the non-clicked PX-PA particles. The results also showed that PA restricted swelling of the PX-PA and PX-PA-AEA particles by acting as a crosslinker. Of the three microgel systems studied, PVP-PA-AEA had the best combination of high AEA incorporation and pH-triggered swelling.
- Farley, Robert,Saunders, Brian R.
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- Surfactant-free one-step synthesis of dual-functional polyurea microcapsules: Contact infection control and drug delivery
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Surface functionalized polyurea microcapsules (MCQ) are synthesized in one step. Dimethyl-dodecyl-(5-hydroxy-pentyl)-ammonium bromide (DAB), a hydroxyl-end-capped quaternary ammonium salt, is synthesized and adopted as a new surfmer for the synthesis of M
- He, Wei,Liu, Song,Gu, Xiaochen
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- One-Step Transformation of Coenzyme A into Analogues by Transamidation
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Several coenzyme A (CoA) analogues are made in a single step under mild conditions via transamidation reactions catalyzed by boric acid in water. This approach offers rapid access to compounds useful for the study of a wide spectrum of enzyme catalyzed re
- Sanichar, Randy,Vederas, John C.
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- Novel menadione hybrids: Synthesis, anticancer activity, and cell-based studies
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A series of novel menadione-based triazole hybrids were designed and synthesized by employing copper-catalyzed azide-alkyne cycloaddition (CuAAC). All the synthesized hybrids were characterized by their spectral data (1H NMR, 13C NMR, IR, and HRMS). The synthesized compounds were evaluated for their anticancer activity against five selected cancer cell lines including lung (A549), prostate (DU-145), cervical (Hela), breast (MCF-7), and mouse melanoma (B-16) using MTT assay. The screening results showed that majority of the synthesized compounds displayed significant anticancer activity. Among the tested compounds, the triazoles 5 and 6 exhibited potent activity against all cell lines. In particular, compound 6 showed higher potency than the standard tamoxifen and parent menadione against MCF-7 cell line. Flow cytometric analysis revealed that compound 6 arrested cell cycle at G0/G1 phase and induced apoptotic cell death which was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin-V-FITC assay. Thus, compound 6 can be considered as lead molecule for further development as potent anticancer therapeutic agent.
- Prasad, Chakka Vara,Nayak, Vadithe Lakshma,Ramakrishna, Sistla,Mallavadhani, Uppuluri Venkata
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- Supramolecular Polymerization Controlled through Kinetic Trapping
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A method of controllable supramolecular polymerization through kinetic trapping is developed. To this end, two bifunctional monomers with cucurbit[7]uril (CB[7]) and adamantane end groups were synthesized. The CB[7]-containing monomer was presaturated with a pH-responsive competitive guest for kinetic control. Then, the kinetics of supramolecular polymerization of the two monomers was easily controlled through the modulation of pH. As a result, supramolecular polymerization was kinetically trapped at certain stages, and supramolecular polymers with different molecular weights were obtained. It is anticipated that this research will enrich the methods of controllable supramolecular polymerization.
- Chen, Hao,Huang, Zehuan,Wu, Han,Xu, Jiang-Fei,Zhang, Xi
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- Template synthesis of tungsten complexes with saturated N-heterocyclic carbene ligands
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Tungsten complex 5 with a coordinated 2-azidoethyl isocyanide ligand reacts with PMe3 at the azido function to give a complex with a coordinated iminophosphorane which upon hydrolysis of the P=N bond yields a complex with an NH,NH-stabilized N-heterocyclic carbene ligand, 7; alkylation of the carbene ring nitrogen atoms gives a complex with an N,N′-dialkylated imidazolidin-2-ylidene ligand, 8. The Royal Society of Chemistry 2005.
- Hahn, F. Ekkehardt,Langenhahn, Volker,Pape, Tania
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- pH-responsive supramolecular nanovalves based on cucurbit[6]uril pseudorotaxanes
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An open and closed case: pH-controllable nanovalves that operate in water have been produced by attaching [2]pseudorotaxanes to the surface of mesoporous silica nanoparticles. The nanovalves are able to contain guest molecules (rhodamine B, red circles) w
- Angelos, Sarah,Yang, Ying-Wei,Patel, Kaushik,Stoddart, J. Fraser,Zink, Jeffrey I.
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- Structure determination of bis{(4Z)-1-(2-azidoethyl)-4-[(pyridin-2-yl) methylidene]-2-thiolatoimidazol-5(4H)-one}dicopper chloride from X-ray powder diffraction data
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The new tridentate organic N2S-type ligand, (4Z)-1-(2- azidoethyl)-4-[(pyridin-2-yl)-methylidene]-2-thioxoimidazol-5(4H)-one (LH), was synthesized. The reaction of LH with copper(II) chloride in a CH 2Cl2/MeOH mixture afforded the coordination compound of the composition L2Cu2Cl (3). The crystal structure of 3 was solved and refined from X-ray powder diffraction data. Complex 3 has a binuclear structure with a short interatomic Cu-Cu distance and one bridging chlorine atom, which is located almost symmetrically with respect to both metal atoms. The planar organic ligands are noncoplanar and are at an angle of 53.56(1) to each other.
- Mironov,Antipov,Beloglazkina,Majouga,Krasnovskaya,Gerasimov,Zyk
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- Template-Directed Synthesis of Porous and Protective Core–Shell Bionanoparticles
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Metal–organic frameworks (MOFs) are promising high surface area coordination polymers with tunable pore structures and functionality; however, a lack of good size and morphological control over the as-prepared MOFs has persisted as an issue in their appli
- Li, Shaobo,Dharmarwardana, Madushani,Welch, Raymond P.,Ren, Yixin,Thompson, Christina M.,Smaldone, Ronald A.,Gassensmith, Jeremiah J.
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- Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas
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The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind 99mTc. The radiolabeled complex, 99mTc-(EST)2DT was obtained in >99% radiochemical purity and 20-48 GBq/μmol of specific activity. RBA assay revealed ~15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ~6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(-) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 μM which was comparable to tamoxifen. The anticancer activity of the ligand is possibly due to the increase in ERβ and suppression of ERα protein levels in gene transcription. The studies reveal the potential of (EST)2DT as diagnostic imaging agent with the additional benefits in therapy. (Chemical Equation Presented).
- Chauhan, Kanchan,Arun, Ashutosh,Singh, Saurabh,Manohar, Murli,Chuttani, Krishna,Konwar, Rituraj,Dwivedi, Anila,Soni, Ravi,Singh, Ajai Kumar,Mishra, Anil K.,Datta, Anupama
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- Efficient electron transporting and panchromatic absorbing FRET cassettes based on aza-BODIPY and perylenediimide towards multiple metal FRET-Off sensing and ratiometric temperature sensing
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Multichromophoric triads 1 and 2 based on aza-BODIPY as the central chromophore and bay-substituted (tetrachloro- and tetraphenoxy-)perylenediimides (PDI) as peripheral chromophores have been designed and synthesized that are panchromatic absorbers and near infrared (NIR) emitters. Both triads 1 and 2 exhibited ~99% F?rster resonance energy transfer (FRET) from the peripheral PDIs to central aza-BODIPY. The excitation energy transfer from PDI to aza-BODIPY was studied via steady state emission, fluorescence quantum yield, time resolved fluorescence emission and theoretical calculations. These studies revealed quantitative singlet excitation energy transfer efficiencies for 1 and 2. Electrochemical studies revealed the strong electron deficient character of these triads and thus electron mobilities of these triads were measured using space charge limited current (SCLC) method. Triads 1 and 2 exhibited appreciable electron mobilities of 2.44 ± 1.70 × 10-3 cm2 V-1 s-1 and 4.00 ± 1.50 × 10-3 cm2 V-1 s-1 respectively, an order of magnitude higher mobility than aza-BODIPY based small molecules reported in the literature. Leveraging upon the dual emission behaviour of these triads, ratiometric FRET sensing as well as ratiometric temperature sensing behaviour were investigated via steady state absorption and fluorescence measurements. Triads 1 and 2 showed remarkable ratiometric FRET-off sensing where the addition of metals such as Co2+ and Fe3+ led to near-quantitative FRET off for both the triads. Triads 1 and 2 also serve as efficient ratiometric temperature sensors with positive temperature coefficients and small temperature sensitivities of ~0.29% °C-1 and ~0.14% °C-1 respectively that suggest the possibility of precise physiological temperature measurements using these triads.
- Rani, Kavita,Pandey, Upendra K.,Sengupta, Sanchita
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supporting information
p. 4607 - 4618
(2021/04/13)
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- Novel diphenylmethyl compounds having mycobacterium tuberculosis inhibitory activity
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The invention relates to novel diphenylmethyl derivatives having mycobacterium tuberculosis inhibitory activity and a preparation method thereof and particularly relates novel diphenylmethyl derivatives having activity for inhibiting replicative and non-replicating mycobacterium tuberculosis and a preparation method thereof. In particular, the invention relates to compounds shown in the formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the variables are as described in the specification. The invention also relates to the preparation method of the compounds and their pharmaceutical compositions and a use of the compounds in preparation of drugs for treating mycobacterium tuberculosis infection-caused diseases.
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Paragraph 0282; 0830
(2019/02/13)
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- An alternative modular 'click-SNAr-click' approach to develop subcellular localised fluorescent probes to image mobile Zn2+
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Zn2+ is involved in a number of biological processes and its wide-ranging roles at the subcellular level, especially in specific organelles, have not yet been fully established due to a lack of tools to image it effectively. We report a new and
- Fang, Le,Trigiante, Giuseppe,Crespo-Otero, Rachel,Philpott, Michael P.,Jones, Christopher R.,Watkinson, Michael
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supporting information
p. 10013 - 10019
(2019/12/23)
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- Method for synthesizing C15 urushiol-based triazole derivatives
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The invention relates to a method for introducing a triazole structure into C15 urushiol-based ether according to a group superposing principle with C15 triene urushiol (3-((8Z,11E,13Z)-pentadeca-8,11,13-trien-1-yl)benzene-1,2-diol) or C15 monoene urushiol ((Z)-3-(pentadec-8-en-1-yl) benzene-1,2-diol) in traditional raw lacquer urushiol in the East Asian Region as a raw material. C15 urushiol-based triazole derivatives can significantly reduce or even eliminate the sensitization of the C15 triene urushiol, and can inhibit the proliferation of liver cancer cells to achieve the attenuation and synergism effects; and the method enlarges the medical application field of the C15 tris(mono)ene urushiol.
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Paragraph 0012
(2019/01/21)
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- Duplex Stem Replacement with bPNA+ Triplex Hybrid Stems Enables Reporting on Tertiary Interactions of Internal RNA Domains
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We report herein the synthesis and DNA/RNA binding properties of bPNA+, a new variant of bifacial peptide nucleic acid (bPNA) that binds oligo T/U nucleic acids to form triplex hybrids. By virtue of a new bivalent side chain on bPNA+, similar DNA affinity and hybrid thermostability can be obtained with half the molecular footprint of previously reported bPNA. Lysine derivatives bearing two melamine bases (K2M) can be prepared on multigram scale by double reductive alkylation with melamine acetaldehyde, resulting in a tertiary amine side chain that affords both peptide solubility and selective base-triple formation with 4 T/U bases; the Fmoc-K2M derivative can be used directly in solid phase peptide synthesis, rendering bPNA+ conveniently accessible. A compact bPNA+binding site of two U6 domains can be genetically encoded to replace existing 6 bp stem elements at virtually any location within an RNA transcript. We thus replaced internal 6 bp RNA stems that supported loop regions with 6 base-triple hybrid stems using fluorophore-labeled bPNA+. As the loop regions engaged in RNA tertiary interactions, the labeled hybrid stems provided a fluorescent readout; bPNA+ enabled this readout without covalent chemical modification or introduction of new structural elements. This strategy was demonstrated to be effective for reporting on widely observed RNA tertiary interactions such as intermolecular RNA-RNA kissing loop dimerization, RNA-protein binding, and intramolecular RNA tetraloop-tetraloop receptor binding, illustrating the potential general utility of this method. The modest 6 bp stem binding footprint of bPNA+ makes the hybrid stem replacement method practical for noncovalent installation of synthetic probes of RNA interactions. We anticipate that bPNA+ structural probes will be useful for the study of tertiary interactions in long noncoding RNAs.
- Miao, Shiqin,Liang, Yufeng,Marathe, Ila,Mao, Jie,Desantis, Chris,Bong, Dennis
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supporting information
p. 9365 - 9372
(2019/06/20)
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- AMPHIPHILIC BIOCONJUGATES OBTAINED FROM XYLAN DERIVATIVES
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The present invention concerns a compound of formula (I): wherein:—n is an integer comprised between 1 and 7;—X1 is in particular a radical of formula —CH2—S—(CH2)k—S—;—A1 is in particular a linear or branched alkylene radical comprising from 2 to 30 carbon atoms, and—X2 is in particular an alkoxy group of formula ORa, wherein Ra is a linear or branched alkyl group comprising from 1 to 10 carbon atoms.
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Paragraph 0110
(2018/02/03)
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- Tri-Orthogonal Scaffolds for the Solid-Phase Synthesis of Peptides
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Multi-orthogonal scaffolds can be useful for the attachment of several different compounds to the same central skeleton. Such compounds can find applications in the development of protein mimics because of their potential to mimic several distant epitopes
- Pícha, Jan,Fabre, Benjamin,Budě?ínsky, Milo?,Hajduch, Jan,Abdellaoui, Mehdi,Jirá?ek, Ji?í
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supporting information
p. 5180 - 5192
(2018/08/01)
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- New ferrocene-based 2-thio-imidazol-4-ones and their copper complexes. Synthesis and cytotoxicity
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Synthesis, characterization (HRMS, NMR, EPR, XANES, UV-Vis spectroscopy, and electrochemistry), DNA and BSA binding and in vitro biological screening of two new ferrocene-incorporated thiohydantoin derivatives (5 and 6) and their copper coordination compounds are reported. The ferrocene-based thiohydantoin derivatives were prepared by copper-catalyzed azide alkyne cycloaddition reactions between alkynyl ferrocenes and 5-(Z)-3-(2-azidoethyl)-2-(methylthio)-5-(pyridin-2-ylmethylene)-1H-imidazol-4H-one. Alkynyl ferrocenes necessary for these syntheses were prepared by new procedures. Intermolecular redox reactions between the ferrocene fragment and copper(+2) coordinated ions were studied by different methods to determine the mechanism and kinetic constants of redox processes. Ferrocene-containing imidazolones (5 and 6) and their copper complexes were also tested for their in vitro cytotoxic activity against MCF-7 and A-549 carcinoma cells, and also against the noncancerous cell line Hek-293. The results showed modest cytotoxicity against the subjected cancer cell line compared with cisplatin. The ability of the obtained compounds to cause DNA degradation and cell apoptosis was investigated, and the distribution of cytosol/pellets was studied by AAS.
- Guk,Krasnovskaya,Dashkova,Skvortsov,Rubtsova,Dyadchenko,Yudina,Kosarev,Soldatov,Shapovalov,Semkina,Vlasova,Pergushov,Shafikov,Andreeva,Melnikov,Zyk,Majouga,Beloglazkina
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supporting information
p. 17357 - 17366
(2019/01/03)
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- Aminotriazole Mn(I) Complexes as Effective Catalysts for Transfer Hydrogenation of Ketones
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A catalytic system based on complexes comprising abundant and cheap manganese together with readily available aminotriazole ligands is reported. The new Mn(I) complexes are catalytically competent in transfer hydrogenation of ketones with 2-propanol as hydrogen source. The reaction proceeds under mild conditions at 80 °C for 20 h with 3 % of catalyst loading using either KOtBu or NaOH as base. Good to excellent yields were obtained for a wide substrate scope with broad functional group tolerance. The obtained results by varying the substitution pattern of the ligand are consistent with an out-sphere mechanism for the H-transfer.
- Martínez-Ferraté, Oriol,Werlé, Christophe,Franciò, Giancarlo,Leitner, Walter
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p. 4514 - 4518
(2018/10/20)
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- N-Phenyl-N-aceto-vinylsulfonamides as Efficient and Chemoselective Handles for N-Terminal Modification of Peptides and Proteins
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A number of vinylsulfonamides were synthesized and screened to identify reagents that can be used to modify octreotide under biological pH and room temperature with improved efficiency. N-Phenyl-N-aceto-vinylsulfonamide exhibits higher reactivity and has emerged as an efficient reagent that has the ability to realize the selective modification of peptides and proteins at the N-terminus via aza-Michael addition. We showed that, after conjugation of peptides and proteins with the reagent containing a bioorthogonal functional group, the derivatives could be further labelled by functionalities, including fluorescent tags, modified drugs and polyethylene glycol (PEG) polymers without the need for prior treatment. Somatostatin, lysozyme, and RNaseA were selectively modified at the N-terminus, which illustrated the application of the method.
- Huang, Rong,Li, Zhihong,Ren, Peiling,Chen, Wenzhang,Kuang, Yuanyuan,Chen, Jiakang,Zhan, Yuexiong,Chen, Hongli,Jiang, Biao
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supporting information
p. 829 - 836
(2018/02/21)
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- Acid/Base-Controllable FRET and Self-Assembling Systems Fabricated by Rhodamine B Functionalized Pillar[5]arene-Based Host-Guest Recognition Motifs
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A novel supramolecular F?ster resonance energy transfer (FRET) system was fabricated by utilizing rhodamine B (RB) functionalized pillar[5]arene (EtP5-RB) and cyano-modified boron dipyrromethene (BDP-CN) based on their host-guest recognition at 5.0 × 10s
- Sun, Jifu,Hua, Bin,Li, Qing,Zhou, Jiong,Yang, Jie
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supporting information
p. 365 - 368
(2018/01/27)
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- Fast and Facile Synthesis of 4-Nitrophenyl 2-Azidoethylcarbamate Derivatives from N-Fmoc-Protected α-Amino Acids as Activated Building Blocks for Urea Moiety-Containing Compound Library
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A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino ac
- Chen, Ying-Ying,Chang, Li-Te,Chen, Hung-Wei,Yang, Chia-Ying,Hsin, Ling-Wei
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supporting information
p. 131 - 136
(2017/04/24)
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- Attractive Interactions between Heteroallenes and the Cucurbituril Portal
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In this paper, we report on the noteworthy attractive interaction between organic azides and the portal carbonyls of cucurbiturils. Five homologous bis-α,-azidoethylammonium alkanes were prepared, where the number of methylene groups between the ammonium groups ranges from 4 to 8. Their interactions with cucurbit[6]uril were studied by NMR spectroscopy, IR spectroscopy, X-ray crystallography, and computational methods. Remarkably, while the distance between the portal plane and most atoms at the guest end groups increases progressively with the molecular size, the β-nitrogen atoms maintain a constant distance from the portal plane in all homologues, pointing at a strong attractive interaction between the azide group and the portal. Both crystallography and NMR support a specific electrostatic interaction between the carbonyl and the azide β-nitrogen, which stabilizes the canonical resonance form with positive charge on the β-nitrogen and negative charge on the β;-nitrogen. Quantum computational analyses strongly support electrostatics, in the form of orthogonal dipole-dipole interaction, as the main driver for this attraction. The alternative mechanism of n a ?€? orbital delocalization does not seem to play a significant role in this interaction. The computational studies also indicate that the interaction is not limited to azides, but generalizes to other isoelectronic heteroallene functions, such as isocyanate and isothiocyanate. This essentially unexploited attractive interaction could be more broadly utilized as a tool not only in relation to cucurbituril chemistry, but also for the design of novel supramolecular architectures.
- Reany, Ofer,Li, Amanda,Yefet, Maayan,Gilson, Michael K.,Keinan, Ehud
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p. 8138 - 8145
(2017/06/28)
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- Divinylsulfonamides as Specific Linkers for Stapling Disulfide Bonds in Peptides
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A new class of N-phenyl-divinylsulfonamides which can be easily prepared have been successfully developed and utilized as efficient linkers in the field of disulfide bond modification. Functional divinylsulfonamides provide opportunities for the specific
- Li, Zhihong,Huang, Rong,Xu, Hongtao,Chen, Jiakang,Zhan, Yuexiong,Zhou, Xianhao,Chen, Hongli,Jiang, Biao
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supporting information
p. 4972 - 4975
(2017/09/23)
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- Discovery of Novel 11-Triazole Substituted Benzofuro[3,2-b]quinolone Derivatives as c-myc G-Quadruplex Specific Stabilizers via Click Chemistry
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The specificity of nucleic acids' binders is crucial for developing this kind of drug, especially for novel G-quadruplexes' binders. Quindoline derivatives have been developed as G-quadruplex stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks. The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was significantly improved, together with an obvious increase on binding affinity. Further cellular and in vivo experiments indicated that the T-BFQs showed inhibitory activity on tumor cells' proliferation, presumably through the down-regulation of transcription of c-myc gene. Our findings broadened the modification strategies of specific G-quadruplex stabilizers.
- Zeng, De-Ying,Kuang, Guo-Tao,Wang, Shi-Ke,Peng, Wang,Lin, Shu-Ling,Zhang, Qi,Su, Xiao-Xuan,Hu, Ming-Hao,Wang, Honggen,Tan, Jia-Heng,Huang, Zhi-Shu,Gu, Lian-Quan,Ou, Tian-Miao
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supporting information
p. 5407 - 5423
(2017/07/22)
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- Small Molecule Recognition Triggers Secondary and Tertiary Interactions in DNA Folding and Hammerhead Ribozyme Catalysis
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We have identified tris(2-aminoethyl)amine (tren)-derived scaffolds with two (t2M) or four (t4M) melamine rings that can target oligo T/U domains in DNA/RNA. Unstructured T-rich DNAs cooperatively fold with the tren derivatives to form hairpin-like structures. Both t2M and t4M act as functional switches in a family of hammerhead ribozymes deactivated by stem or loop replacement with a U-rich sequence. Catalysis of bond scission in these hammerhead ribozymes could be restored by putative t2M/t4M refolding of stem secondary structure or tertiary bridging interactions between loop and stem. The simplicity of the t2M/t4M binding site enables programming of allostery in RNAs, recoding oligo-U domains as potential sites for secondary structure or tertiary contact. In combination with a facile and general method for installation of the t2M motif on primary amines, the method described herein streamlines design of synthetic allosteric riboswitches and small molecule-nucleic acid complexes.
- Mao, Jie,Desantis, Chris,Bong, Dennis
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supporting information
p. 9815 - 9818
(2017/08/02)
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- Synthesis of new triazole based imidazo[1,2-a]pyrazine-benzimidazole conjugates: H-bonding assisted FRET efficient ratiometric detection of pyrophosphate
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Triazole tethered imidazo[1,2-a]pyrazine-benzimidazole conjugates 13-38 has been synthesized by click and Suzuki-Miyaura cross coupling reactions at C-8 and C-6 positions, respectively. The research findings clearly predicted that by modification of electronic structure of the receptor, the sensitivity of the recognition process could be modified. Compound 24 with hydroxyphenyl substituent, showed stronger binding to the pyrophosphate than other compounds. Compound 24 has been used as selective probe for ratiometric detection of pyrophosphate amongst the other anions. The binding event of compound 24 toward PPi has been successfully evaluated by absorption and emission spectroscopy as well as NMR titration method. The compound 24 showed H-bonding assisted facilitation of FRET phenomenon in the presence of PPi.
- Goel, Richa,Luxami, Vijay,Paul, Kamaldeep
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p. 102 - 109
(2017/09/02)
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- Dual Chemical Modification of a Polytheonamide Mimic: Rational Design and Synthesis of Ion-Channel-Forming 48-mer Peptides with Potent Cytotoxicity
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Polytheonamide B (1) is a natural peptide that displays potent cytotoxicity against P388 mouse leukemia cells (IC50=0.098 nm). Linear 48-mer 1 is known to form monovalent cation channels on binding to lipid bilayers. We previously developed a fully synthetic route to 1, and then achieved the design and synthesis of a structurally simplified analogue of 1, namely, dansylated polytheonamide mimic 2. Although the synthetically more accessible 2 was found to emulate the channel function of 1, its cytotoxicity was decreased 120-fold. Herein, the chemical preparation and biological evaluation of seven analogues 3-9 of 2 are reported. Compounds 3-9 were modified at their N terminus and/or the side chain of residue 44 of 2 to alter their physicochemical properties. The total synthesis of 3-9 was accomplished in a unified fashion by a combination of solid-phase and solution-phase chemistry. Systematic evaluation of the hydrophobicities, single-channel currents, ion-exchange activities, and cytotoxicities of 3-9 revealed that their hydrophobicities are correlated with the total magnitude of ion exchange and determine their cytotoxic potency. Consequently, the most hydrophobic analogue 9 exhibited the lowest IC50 value, which is comparable to that of 1. Therefore, these results clarified that the bioactivity of the polytheonamide-based peptides can be rationally controlled by changing their hydrophobicity at the N and C termini of the 48-amino-acid sequence.
- Hayata, Atsushi,Itoh, Hiroaki,Matsutaka, Shoko,Inoue, Masayuki
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supporting information
p. 3370 - 3377
(2016/03/05)
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- Design, Synthesis, and Structural Optimization of Lycorine-Derived Phenanthridine Derivatives as Wnt/β-Catenin Signaling Pathway Agonists
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Lycorine is a benzylphenethylamine-type alkaloid member of the Amaryllidaceae family. A lycorine derivative, HLY78, was previously identified as a new Wnt/β-catenin signaling pathway agonist that targets the DAX domain of axin. Herein, the structural opti
- Chen, Duo-Zhi,Jing, Chen-Xu,Cai, Jie-Yun,Wu, Ji-Bo,Wang, Sheng,Yin, Jun-Lin,Li, Xiao-Nian,Li, Lin,Hao, Xiao-Jiang
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p. 180 - 188
(2016/02/05)
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- A can be used as signal route Wnt activator compound and its preparation and use
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The invention provides compound used as a Wnt signal pathway activator, and a preparation and an application thereof. The compound is a compound of formula (I) or formula (II). The compound can be used for preparing medicines for adjusting a classic Wnt signal pathway, and can also be used for researching the classic Wnt signal pathway. The compound also provides a new idea for screening the medicines for adjusting the Wnt signal pathway and medicines for preventing and treating classic Wnt signal pathway related diseases, and researching the application of the Wnt signal pathway in stem cells.
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Paragraph 0094; 0111; 0112; 0113; 0114
(2016/10/10)
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- Phenanthridine Derivatives, Preparation Methods and Uses Thereof
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The present invention relates to the pharmaceutical field, in particular to a phenanthridine derivative as shown in general formula (1) a pharmaceutical composition comprising the derivative, its preparation method, and its uses in manufacture of a medica
- -
-
Paragraph 0136
(2016/04/19)
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- Synthesis of energy transfer cassettes via click and Suzuki-Miyaura cross coupling reactions
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Novel cassettes capable of energy transfer involving simple synthetic methods viz., copper catalyzed azide-alkyne cycloaddition (click reaction) at the C-8 position and palladium catalyzed Suzuki-Miyaura cross coupling at the C-6 position have been represented. The resulting imidazo[1,2-a]pyrazine-triazole bridged coumarin cassettes are capable of energy transfer from a donor core to an acceptor moiety.
- Goel, Richa,Luxami, Vijay,Paul, Kamaldeep
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p. 37664 - 37671
(2016/05/19)
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- Synthesis and Evaluation of a Library of Trifunctional Scaffold-Derived Compounds as Modulators of the Insulin Receptor
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We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds were proposed to mimic insulin receptor (IR)-binding epitopes in the insulin molecule and bind to and activate this receptor. This work has enabled us to test our synthetic and biological methodology and to prove its robustness and reliability for the solid-phase synthesis and testing of combinatorial libraries of the trifunctional scaffold-derived compounds. Our effort resulted in the discovery of two compounds, which were able to weakly induce the autophosphorylation of IR and weakly bind to this receptor at a 0.1 mM concentration. Despite these modest biological results, which well document the well-known difficulty in modulating protein-protein interactions, this study represents a unique example of targeting the IR with a set of nonpeptide compounds that were specifically designed and synthesized for this purpose. We believe that this work can open new perspectives for the development of next-generation insulin mimetics based on the scaffold structure.
- Fabre, Benjamin,Pícha, Jan,Vaněk, Václav,Selicharová, Irena,Chrudinová, Martina,Collinsová, Michaela,?áková, Lenka,Budě?ínsky, Milo?,Jirá?ek, Ji?í
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supporting information
p. 710 - 722
(2016/12/22)
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- A Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery
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A novel "collaborative assembly" approach was reported for the synthesis of an siRNA delivery system via a combination of an electrostatically driven physical assembly and a facile click reaction-mediated chemical assembly, which showed various advantages
- Sun, Qiong,Kang, Zisheng,Xue, Lingjing,Shang, Yunkai,Su, Zhigui,Sun, Hongbin,Ping, Qineng,Mo, Ran,Zhang, Can
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supporting information
p. 6000 - 6010
(2015/05/27)
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- A base having a base or codissolution deriv. perfluoroalkyne nonazide and its polymer
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PROBLEM TO BE SOLVED: To provide an isopropyl acrylamide derivative having an azido group or an alkyne group. SOLUTION: The isopropyl acrylamide derivative having an azido group or an alkyne group is represented by formula (1). In the formula: X is a hydrogen atom or a 1-6C straight or branched chain alkyl group; Y is any functional group selected from the group consisting of 1-6C alkyl, amide, ester, ether, ketone, triazole, hydrazone, disulfide, and silane groups; and Z is an azido group or an alkyne group. COPYRIGHT: (C)2013,JPOandINPIT
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Paragraph 0046
(2016/12/12)
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- A disulfide intercalator toolbox for the site-directed modification of polypeptides
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A disulfide intercalator toolbox was developed for site-specific attachment of a broad variety of functional groups to proteins or peptides under mild, physiological conditions. The peptide hormone somatostatin (SST) served as model compound for intercalation into the available disulfide functionalization schemes starting from the intercalator or the reactive SST precursor before or after bioconjugation. A tetrazole-SST derivative was obtained that undergoes photoinduced cycloaddition in mammalian cells, which was monitored by live-cell imaging.
- Wang, Tao,Wu, Yuzhou,Kuan, Seah Ling,Lamla, Markus,Ng, David Y. W.,Arzt, Matthias,Thomas, Jessica,Weil, Tanja,Dumele, Oliver,Mueller, Jan O.,Barner-Kowollik, Christopher
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supporting information
p. 228 - 238
(2015/02/19)
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- Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors
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The protein N-terminal methyltransferase 1 (NTMT1) methylates the α-N-terminal amines of proteins. NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects. Therefore, NTMT1 inhibitors could be potential anticancer therapeutics. This study describes the design and synthesis of the first inhibitor targeting NTMT1. A novel bisubstrate analogue (NAM-TZ-SPKRIA) was shown to be a potent inhibitor (Ki = 0.20 μM) for NTMT1 and was selective versus protein lysine methyltransferase G9a and arginine methyltransferase 1. NAM-TZ-SPKRIA was found to exhibit a competitive inhibition pattern for both substrates, and mass spectrometry experiments revealed that the inhibitor substantially suppressed the methylation progression. Our results demonstrate the feasibility of using a triazole group to link an S-adenosyl-l-methionine analog with a peptide substrate to construct bisubstrate analogues as NTMT1 potent and selective inhibitors. This study lays a foundation to further discover small molecule NTMT1 inhibitors to interrogate its biological functions, and suggests a general strategy for the development of selective protein methyltransferase inhibitors. This journal is
- Zhang, Gang,Richardson, Stacie Lynn,Mao, Yunfei,Huang, Rong
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supporting information
p. 4149 - 4154
(2015/04/14)
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- Synthesis of substituted imidazolines by an Ugi/Staudinger/aza-Wittig sequence
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A series of 2-(acetamide-2-yl)-imidazolines (II) with 5 points of diversity were prepared by an Ugi-4CR-Staudinger-aza-Wittig-sequence starting from simple azidoalkylamines. The intramolecular aza-Wittig cyclization between the iminophosphane and the tertiary amide of the Ugi product (I) was effected by short microwave irradiation. Competitive cyclization to the secondary amide was not relevant, however, in some cases subsequent formation of the bicyclic ortho-amidines (III) was observed.
- Welsch, Sebastian J.,Umkehrer, Michael,Kalinski, Cedric,Ross, Günther,Burdack, Christoph,Kolb, Jürgen,Wild, Martina,Ehrlich, Anja,Wessjohann, Ludger A.
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supporting information
p. 1025 - 1029
(2015/02/19)
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- NOVEL KLK4 INHIBITORS
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The present invention relates to novel compounds and probes which have a common chemical structure necessary to obtain potent inhibitory activity against KLK4 and/or may be used for the detection of KLK4 peptides and their activity. It further relates to the use of these compounds and methods for inhibiting and/or detecting KLK4 activity in vitro and in vivo by making use of said probes or inhibitors. The compounds of the invention differ from prior art compounds at least in the presence of phenyl guanidine (instead of e.g. benzyl guanidine) and/or the presence of a heteroatom in the tail group, their combined presence unexpectedly leading to potent and selective KLK4 inhibitory activity.
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Page/Page column 28; 39; 40
(2015/12/18)
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- Expanding the scope of strained-alkyne chemistry: A protection-deprotection strategy via the formation of a dicobalt-hexacarbonyl complex
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A protection-deprotection strategy for strained alkynes used for bioorthogonal chemistry is reported. A strained alkyne can be protected with dicobalt-octacarbonyl and we demonstrate for the first time that a strained alkyne can be re-formed and isolated
- Gobbo, Pierangelo,Romagnoli, Tommaso,Barbon, Stephanie M.,Price, Jacquelyn T.,Keir, Jennifer,Gilroy, Joe B.,Workentin, Mark S.
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supporting information
p. 6647 - 6650
(2015/04/14)
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- AMINO ACID DERIVATIVES
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There are provided amino acid derivatives of formula V and VI as defined herein which are pyrrolysine analogs for use in bioconjugation processes.
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Page/Page column 19
(2014/04/04)
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- Helical polycarbodiimide cloaking of carbon nanotubes enables inter-nanotube exciton energy transfer modulation
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The use of single-walled carbon nanotubes (SWCNTs) as near-infrared optical probes and sensors require the ability to simultaneously modulate nanotube fluorescence and functionally derivatize the nanotube surface using noncovalent methods. We synthesized a small library of polycarbodiimides to noncovalently encapsulate SWCNTs with a diverse set of functional coatings, enabling their suspension in aqueous solution. These polymers, known to adopt helical conformations, exhibited ordered surface coverage on the nanotubes and allowed systematic modulation of nanotube optical properties, producing up to 12-fold differences in photoluminescence efficiency. Polymer cloaking of the fluorescent nanotubes facilitated the first instance of controllable and reversible internanotube exciton energy transfer, allowing kinetic measurements of dynamic self-assembly and disassembly.
- Budhathoki-Uprety, Januka,Jena, Prakrit V.,Roxbury, Daniel,Heller, Daniel A.
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supporting information
p. 15545 - 15550
(2014/12/12)
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- Side chain impacts on pH- and thermo-responsiveness of tertiary amine functionalized polypeptides
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The systemic investigation of the structural impacts of side chains on the pH- and thermo-responsiveness of tertiary amine functionalized poly(l-glutamate)s (TA-PGs) was carried out. The TA-PGs polymers were effectively synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition click reaction of azido tertiary amines with poly(γ-propargyl-l-glutamate) (PPLG). Turbimetric measurements were performed to characterize the pH- and temperature-induced phase transition of TA-PGs in aqueous solution, which suggested a structural dependence of the properties on the N-substituted groups and the "linkers" between 1,2,3-triazole ring and the tertiary amine groups in the side chains. In detail, the pH responsive properties of TA-PGs were basically determined by the hydrophobicity of the N-substituted groups in the side chains and the pH transition point (pHt) decreased as the increasing hydrophobicity of the N-substituted groups, while the temperature-responsiveness of TA-PGs were affected by either the N-substituted groups or the "linkers." TA-PGs with a moderate N-substituted amine group (e.g., DEA, PR, and PD) or a branched "linker" (e.g., iso-propylene and 2-methylpropylene group) were more likely to express the LCST-type phase transition tuned by pH variation. These structure-property relationships revealed in this study would help to develop the applications of TA-PGs in smart drug delivery systems. Copyright
- Xiao, Chunsheng,Cheng, Yilong,Zhang, Yu,Ding, Jianxun,He, Chaoliang,Zhuang, Xiuli,Chen, Xuesi
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p. 671 - 679
(2014/02/14)
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- Visualizing the chain-flipping mechanism in fatty-acid biosynthesis
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The acyl carrier protein (ACP) from fatty acid synthases sequesters elongating products within its hydrophobic core, but this dynamic mechanism remains poorly understood. We exploited solvatochromic pantetheine probes attached to ACP that fluoresce when s
- Beld, Joris,Cang, Hu,Burkart, Michael D.
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supporting information
p. 14456 - 14461
(2015/02/19)
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- Click-assembled, oxygen-sensing nanoconjugates for depth-resolved, near-infrared imaging in a 3-D cancer model
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Hypoxia is an important contributing factor to the development of drug-resistant cancer, yet few nonperturbative tools exist for studying oxygenation in tissues. While progress has been made in the development of chemical probes for optical oxygen mapping, penetration of such molecules into poorly perfused or avascular tumor regions remains problematic. A click-assembled oxygen-sensing (CAOS) nanoconjugate is reported and its properties demonstrated in an in vitro 3D spheroid cancer model. The synthesis relies on the sequential click-based ligation of poly(amidoamine)-like subunits for rapid assembly. Near-infrared confocal phosphorescence microscopy was used to demonstrate the ability of the CAOS nanoconjugates to penetrate hundreds of micrometers into spheroids within hours and to show their sensitivity to oxygen changes throughout the nodule. This proof-of-concept study demonstrates a modular approach that is readily extensible to a wide variety of oxygen and cellular sensors for depth-resolved imaging in tissue and tissue models. Embracing the CAOS: A click-assembled oxygen-sensing (CAOS) nanoconjugate was developed for studying oxygenation in complex tissue regions. Click-based ligation of preassembled subunits (shown as colored segments) was used to create tissue-penetrating near-infrared-emissive molecular probes, which enable oxygen-sensitive imaging within a 3D tumor spheroid model through the use of confocal phosphorescence microscopy.
- Nichols, Alexander J.,Roussakis, Emmanuel,Klein, Oliver J.,Evans, Conor L.
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supporting information
p. 3671 - 3674
(2014/04/17)
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- Organocatalytic ring-opening polymerization of cyclic esters mediated by highly active bifunctional iminophosphorane catalysts
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Highly active bifunctional iminophosphorane catalysts have been applied to the organocatalytic ring-opening polymerization (ROP) of l-lactide (LA), δ-valerolactone (VL), and ε-caprolactone (CL). LA polymerization using catalyst 2 at 1 mol % loading rapidl
- Goldys, Anna M.,Dixon, Darren J.
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p. 1277 - 1284
(2014/03/21)
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- Construction of targeting-clickable and tumor-cleavable polyurethane nanomicelles for multifunctional intracellular drug delivery
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New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.
- Song, Nijia,Ding, Mingming,Pan, Zhicheng,Li, Jiehua,Zhou, Lijuan,Tan, Hong,Fu, Qiang
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p. 4407 - 4419
(2014/01/06)
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- Modular synthesis, spectroscopic characterization and in situ functionalization using "click" chemistry of azide terminated amide containing self-assembled monolayers
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A general and modular synthetic route is developed for the synthesis of azidoalkylthiol molecules, which contain an amide functional group, from common and easily available precursors. SAMs (self-assembled monolayers) formed by these amide containing azidoalkylthiols are characterised by attenuated total reflectance FTIR spectroscopy, X-ray photoelectron spectroscopy, contact angle goniometry and surface enhanced Raman spectroscopy. Signature peaks are identified in the data which allows direct observation of all the functional groups on Au electrodes bearing these monolayers. The terminal azide group is functionalised with electroactive ferrocene group in situ, using "click" chemistry. An alkyne bearing heme derivative is covalently attached using the same technique resulting in O2 reducing electrodes.
- Bandyopadhyay, Sabyasachi,Mukherjee, Sohini,Dey, Abhishek
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p. 17174 - 17187
(2013/09/24)
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