- Lysine-Based C60-Fullerene Nanoconjugates for Monomethyl Fumarate Delivery: A Novel Nanomedicine for Brain Cancer Cells
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In the present study, water-soluble lysine-based C60-fullerene nanoconjugates (CF-LYS-TEG-MMF) were synthesized using a biodegradable linker for the better delivery of monomethyl fumarate (MMF) employing Prato reaction. CF-LYS-TEG-MMF resulted
- Kumar, Manish,Sharma, Gajanand,Kumar, Rajendra,Singh, Bhupinder,Katare, Om Prakash,Raza, Kaisar
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- 1H NMR investigation of solvent effects in aromatic stacking interactions
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One of the marquis challenges in modern Organic Chemistry concerns the design and synthesis of abiotic compounds that emulate the exquisite complex structures and/or functions of biological macromolecules. Oligomers possessing the propensity to adopt well-defined compact conformations, or foldamers, have been attained utilizing hydrogen bonding, torsional restriction, and solvophobic interactions. In this laboratory, aromatic electron donor-acceptor interactions have been exploited in the design of aedamers-foldamers that adopt a novel, pleated secondary structure in aqueous solution. Herein is reported detailed 1H NMR binding studies of aedamer monomers that were carried out in solvents and solvent mixtures covering a broad polarity range. Curve-fitting analysis of the binding data using a model that incorporated the formation of higher order and self-associated complexes yielded a linear free energy relationship between the free energy of complexation and the empirical solvent polarity parameter, ET(30). From these studies, the association of electron-rich and electron-deficient aedamer monomers was seen to be driven primarily by hydrophobic interactions in polar solvents. However, the magnitude of these interactions is modulated to a significant extent by the geometry of the donor-acceptor complex, which, in turn, is dictated by the electrostatic complementarity between the electron-deficient and electron-rich aromatic faces of the monomers.
- Cubberley,Iverson
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- Honeycomb membranes prepared from 3-O-amino acid functionalized cellulose derivatives
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The development of value-added wood-derived polymer products is of significant importance. Of particular interest is the synthesis of advanced bioactive cellulosic materials. In the present research, novel cellulosic honeycomb films are reported. Cellulos
- Xu, William Z.,Bar-Nir, Batia Ben-Aroya,Kadla, John F.
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- A novel biocompatible europium ligand for sensitive time-gated immunodetection
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We describe the synthesis of a novel hydrophilic derivative of a tetradentate β-diketone europium ligand that was used to prepare an immunoconjugate probe against Giardia lamblia cysts. We used a Gated Autosynchronous Luminescence Detector (GALD) to obtain high quality delayed luminescence images of cells 30-fold faster than ever previously reported.
- Sayyadi, Nima,Connally, Russell E.,Try, Andrew
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- Vesicle aggregation by multivalent ligands: Relating crosslinking ability to surface affinity
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In an effort to improve the stability of our tissue-mimetic vesicle aggregates, we have investigated how increasing the valency of our multivalent crosslinking ligand, poly-l-histidine, affected both the extent of vesicle aggregation and the affinity of t
- Wang, Xi,Mart, Robert J.,Webb, Simon J.
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- Catalytic Asymmetric Direct-Type 1,4-Addition Reactions of Simple Amides
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The development of catalytic asymmetric direct-type reactions of less acidic carbonyl compounds such as amides and esters has been a challenging theme in organic chemistry for decades. Here we describe the asymmetric direct 1,4-addition reactions of simple amides with α,β-unsaturated carbonyl compounds using a catalytic amount of a novel chiral catalyst consisting of a potassium base and a macrocyclic chiral crown ether. The desired 1,5-dicarbonyl compounds were obtained in high yields with excellent diastereo- and enantioselectivities. This is the first example of a highly enantioselective catalytic direct-type reaction of simple amides. In addition, the structure of the chiral potassium catalyst has been investigated by X-ray crystallographic, dynamic 1H NMR, and MALDI-TOF MS analyses.
- Suzuki, Hirotsugu,Sato, Io,Yamashita, Yasuhiro,Kobayashi, Shu
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- BisPNA targeting to DNA: Effect of neutral loop on DNA duplex strand invasion by aepPNA-N7G/aepPNA-C substituted peptide nucleic acids
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N7-Alkyl-substituted guanine (N7G) as a CH+ mimic has been introduced into aminoethylglycyl PNA (aegPNA) forming a hairpin through a neutral linker derived from bis(tetraethylene) glycol (teg-teg). These form pH-independent PNA2:DNA
- Shirude, Pravin S.,Kumar, Vaijayanti A.,Ganesh, Krishna N.
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- Selenacrown Macrocycle in Aqueous Medium: Synthesis, Redox-Responsive Self-Assembly, and Enhanced Disulfide Formation Reaction
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Organic selenides are famous for their coordination and catalytic functions in the organic phase, albeit challenging for aqueous medium. Herein, the combination of a hydrophilic body of crown ether and substitution of one oxygen atom with a selenium one provides a new type of design route for organic selenide entities with charming functions in aqueous solution. The selenacrown ether C9Se presented here intrinsically shows an amphiphile-like property. Its nanosphere structure in water readily expands the catalysis of organic selenide to aqueous substrates in thiol/disulfide conversion.
- Shang, Jie,Li, Bo,Shen, Xin,Pan, Tiezheng,Cui, Zhiliyu,Wang, Yangxin,Ge, Yan,Qi, Zhenhui
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- Precise macroscopic supramolecular assembly of photopatterned hydrogels
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Here we demonstrate that a precise macroscopic supramolecular assembly (MSA) can be achieved using a surface photopatterning strategy. The electrostatic interaction of the photopatterned polyelectrolytes drives hydrogel cuboids to form a stable MSA on a m
- Bao, Chunyan,Pang, Shihao,Wang, Xuebin,Xiang, Yanxing,Xue, Yuan,Ye, Kai,Zhu, Linyong
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Read Online
- Discovery of novel potent covalent inhibitor-based EGFR degrader with excellent in vivo efficacy
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Although several Epidermal growth factor receptor (EGFR) inhibitors have been approved for the treatment of non-small-cell lung cancers (NSCLC), acquired drug resistance and side effects largely encumbered their application in clinic. The emerging technology Proteolysis targeting chimera (PROTAC) could be an alternative strategy to overcome these problems. Here, we reported the discovery of Dacomitinib-based EGFR degraders. Promising compound 13 can effectively induce degradation of EGFRdel19 with DC50 value of 3.57 nM in HCC-827 cells, but not to other EGFR mutant, wild-type EGFR protein and the same family receptors (HER2 and HER4). Of note, 13 is the first EGFR-PROTAC to evaluate antitumor effect in vivo, and exhibited excellent antitumor efficacy (TGI = 90%) at a dose of 30 mg/kg without causing observable toxic effects. The preliminary mechanism study demonstrated that 13 can efficiently induce EGFR protein degradation through ubiquitin proteasome pathway and inhibit phosphorylation of downstream pathways in vitro and in vivo, which indicated that 13 exerted antitumor effect by degradation of EGFR protein in tumor tissue. Overall, our study provided further evidence to validate EGFR-PROTACs as a promising strategy for lung cancer therapy.
- Cui, Jiaqi,Du, Yu,Huang, Lei,Niu, Jing,Shi, Shi,Xu, Yungen,Zhu, Qihua
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supporting information
(2022/01/26)
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- An air-tolerant polymer gel-immobilized iridium photocatalyst with pumping recyclability properties
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A novel methacrylate-based cross-linked polymer gel bearing an iridium photocatalyst showed air tolerance and pumping recyclability features through its tunable swelling and deswelling ability. The photocatalytic activity of the polymer gel was demonstrated through an E-to-Z isomerisation reaction and in an azide-alkene [2+3] cycloaddition.
- Abramov, Alex,Díaz Díaz, David,Maiti, Binoy,Reiser, Oliver
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supporting information
p. 7762 - 7765
(2021/08/13)
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- Gold-Catalyzed Amide/Carbamate-Linked N, O-Acetal Formation with Bulky Amides and Alcohols
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A gold-catalyzed N,O-acetal formation was established to construct an amide/carbamate-linked N,O-acetal substructure with bulky alcohols. The acyliminium cation species generated from o-alkynylbenzoic acid ester in the presence of a gold catalyst is highly reactive and underwent nucleophilic attack of various bulky alcohols and phenols at room temperature under neutral conditions, leading to the corresponding N,O-acetals in yields of 34-89% with good functional group tolerance.
- Ohsawa, Kosuke,Ochiai, Shota,Kubota, Junya,Doi, Takayuki
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p. 1281 - 1291
(2021/01/14)
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- Solvent-Driven Supramolecular Wrapping of Self-Assembled Structures
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Self-assembly relies on the ability of smaller and discrete entities to spontaneously arrange into more organized systems by means of the structure-encoded information. Herein, we show that the design of the media can play a role even more important than
- Moreno-Alcántar, Guillermo,Aliprandi, Alessandro,Rouquette, Remi,Pesce, Luca,Wurst, Klaus,Perego, Claudio,Brüggeller, Peter,Pavan, Giovanni M.,De Cola, Luisa
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supporting information
p. 5407 - 5413
(2021/01/26)
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- Novel supramolecular host macrocycle and preparation method thereof
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The invention discloses a preparation method of a novel supramolecular host macrocycle compound, which is prepared by taking methyl 2,5-dihydroxybenzoate, tetraethylene glycol and dithio tetrathiafulvalene as raw materials through a series of chemical reactions. The supramolecular host macrocycle has a better cavity structure and abundant complexing sites, and can effectively complex related guest molecules. Due to the unique redox property of tetrathiafulvalene, the supermolecule host macrocycle has potential application value in the fields of intelligent response molecular switches and the like. In addition, the supramolecular host macrocycle contains ester group active sites, so that the host macrocycle can be structurally modified, and the topological structure of the supramolecular host macrocycle is further enriched.
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Paragraph 0028-0031
(2021/07/21)
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- Novel cross-linked molecule for protein targeted transportation as well as preparation method and application of novel cross-linked molecule
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The invention discloses a novel cross-linked molecule for protein targeted transportation as well as a preparation method and application of the novel cross-linked molecule, and belongs to the technical field of protein targeted transportation. The novel
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Paragraph 0048-0052; 0073-0077
(2021/08/14)
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- Optical Manipulation of Subcellular Protein Translocation Using a Photoactivatable Covalent Labeling System
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The photoactivatable chemically induced dimerization (photo-CID) technique for tag-fused proteins is one of the most promising methods for regulating subcellular protein translocations and protein–protein interactions. However, light-induced covalent protein dimerization in living cells has yet to be established, despite its various advantages. Herein, we developed a photoactivatable covalent protein-labeling technology by applying a caged ligand to the BL-tag system, a covalent protein labeling system that uses mutant β-lactamase. We further developed CBHD, a caged protein dimerizer, using caged BL-tag and HaloTag ligands, and achieved light-induced protein translocation from the cytoplasm to subcellular regions. In addition, this covalent photo-CID system enabled quick protein translocation to a laser-illuminated microregion. These results indicate that the covalent photo-CID system will expand the scope of CID applications in the optical manipulation of cellular functions.
- Kowada, Toshiyuki,Arai, Keisuke,Yoshimura, Akimasa,Matsui, Toshitaka,Kikuchi, Kazuya,Mizukami, Shin
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supporting information
p. 11378 - 11383
(2021/04/09)
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- Isorhamnetin biotin probe, synthesis method and application thereof
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The invention relates to an isorhamnetin biotin probe, a synthesis method and application thereof, the probe takes isorhamnetin as a reaction group and biotin as an affinity tag, and has the structureshown as the formula in the specification, wherein X is
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Paragraph 0044; 0054-0059
(2021/02/10)
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- Synthesis of 3′-O-Alkyl Homologues and a Biotin Probe of Isorhamnetin and Evaluation of Cytotoxic Efficacy on Cancer Cells
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Isorhamnetin is a natural flavonoid which shows a variety of biological activities such as antioxidant, anti-inflammatory and antitumor. In order to identify the cellular binding protein of isorhamnetin as potential anti-cancer target, we first synthesize
- Tursumamat, Nafisa,Yang, Zhuojin,Zheng, Yi,Zhu, Mingyan
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- Design, synthesis and biological evaluation of a halogenated phenazine-erythromycin conjugate prodrug for antibacterial applications
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There is a significant need for new antibacterial agents as pathogenic bacteria continue to threaten human health through the acquisition of resistance and tolerance towards existing antibiotics. Over the last several years, our group has been developing
- Yang, Hongfen,Liu, Ke,Jin, Shouguang,Huigens III, Robert W.
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supporting information
p. 1483 - 1487
(2021/03/01)
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- PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
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The invention provides a PROTAC compound represented by formula I and used for targeted degradation of IDO1, and a pharmaceutically acceptable salt, a hydrate or a solvate thereof. In the formula I, Xrepresents -CH2 or -C = O, Y represents -CH2 or -C= O, and n is a natural number from 2 to 9. The PROTAC compound for targeted degradation of the IDO1 has efficient activity of targeted degradation of the IDO1 protein.
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- Discovery of a new class of PROTAC BRD4 degraders based on a dihydroquinazolinone derivative and lenalidomide/pomalidomide
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BRD4 has emerged as an attractive target for anticancer therapy. However, BRD4 inhibitors treatment leads to BRD4 protein accumulation, together with the reversible nature of inhibitors binding to BRD4, which may limit the efficacy of BRD4 inhibitors. To address these problems, a protein degradation strategy based on the proteolysis targeting chimera (PROTAC) technology has been developed to target BRD4 recently. Herein, we present our design, synthesis and biological evaluation of a new class of PROTAC BRD4 degraders, which were based on a potent dihydroquinazolinone-based BRD4 inhibitor compound 6 and lenalidomide/pomalidomide as ligand for E3 ligase cereblon. Gratifyingly, several compounds showed excellent inhibitory activity against BRD4, and high anti-proliferative potency against human monocyte lymphoma cell line THP-1. Especially, compound 21 (BRD4 BD1, IC50 = 41.8 nM) achieved a submicromolar IC50 value of 0.81 μM in inhibiting the growth of THP-1 cell line, and was 4 times more potent than compound 6. Moreover, the mechanism study established that 21 could effectively induce the degradation of BRD4 protein and suppression of c-Myc. All of these results suggested that 21 was an efficacious BRD4 degrader for further investigation.
- Zhang, Fangqing,Wu, Zhenwei,Chen, Pan,Zhang, Jian,Wang, Tao,Zhou, Jinpei,Zhang, Huibin
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- BIVALENT TARGETED CONJUGATES
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The invention provides conjugates that comprise a bivalent targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates, compositions comprising the bidentate targeting ligands and the conjugates, as well as methods for targeting therapeutic nucleic acids with the bidentate conjugates. The conjugates are useful to target therapeutic nucleic acids.
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Page/Page column 37
(2020/05/28)
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- THERAPEUTIC METHODS
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The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
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Page/Page column 97; 99; 204; 207-208
(2020/05/28)
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- Vitamin-guanosine monophosphate conjugates for: In vitro transcription priming
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Expanding the catalytic repertoire of ribozymes to include vitamin synthesis requires efficient labelling of RNA with the substrate of interest, prior to in vitro selection. For this purpose, we rationally designed and synthesized six GMP-conjugates carry
- Bande, Omprakash,Groaz, Elisabetta,Herdewijn, Piet,Marlière, Philippe,Papastavrou, Nikolaos
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supporting information
p. 2787 - 2790
(2020/03/17)
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- Phototriggered labeling and crosslinking by 2-nitrobenzyl alcohol derivatives with amine selectivity
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Here we report the use of 2-nitrobenzyl alcohol (NB) as a photoreactive group with amine selectivity and explore its applications for photoaffinity labeling and crosslinking of biomolecules. This work confirms that NB is an efficient photoreactive group a
- Wang, Chenxi,Liu, Yuan,Bao, Chunyan,Xue, Yuan,Zhou, Yaowu,Zhang, Dasheng,Lin, Qiuning,Zhu, Linyong
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supporting information
p. 2264 - 2267
(2020/03/04)
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- PYRROLO[2,3-B]PYRIDIN DERIVATIVES AS INHIBITORS OF INFLUENZA VIRUS REPLICATION
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Provided herein are compounds of Formula A, B or C that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.
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Paragraph 00288
(2020/02/16)
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- Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
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The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
- Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
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supporting information
(2020/07/21)
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- Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli
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High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sh
- Atchimnaidu, Siriki,Golla, Murali,Harikrishnan, Kaloor S.,Kalathil, Jemshiya,Krishna, Jithu,Krishnan, Nithiyanandan,Kumar, Nilima Manoj,Perumal, Devanathan,Varghese, Reji,Vijayan, Dileep K.
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supporting information
(2020/01/25)
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- Pegylated triarylmethanes: Synthesis, antimicrobial activity, anti-proliferative behavior and in silico studies
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We describe herein the synthesis, characterization and biological studies of novel PEGylated triarylmethanes. Non-symmetrical and symmetrical triarylmethanes series have been synthesized by Friedel-Crafts hydroxyalkylation or directly from bisacodyl respectively followed by a functionalization with PEG fragments in order to increase bioavailability and biological effectiveness. The antimicrobial activity was investigated against Gram-positive and Gram-negative foodborne pathogens and against Candida albicans, an opportunistic pathogenic yeast. The anti-biocidal activity was also studied using Staphylococcus aureus as a reference bacterium. Almost all PEGylated molecules displayed an antifungal activity comparable with fusidic acid with MIC values ranging from 6.25 to 50 μg/mL. Compounds also revealed a promising antibiofilm activity with biofilm eradication percentages values above 80% for the best molecules (compounds 4d and 7). Compounds 7 and 8b showed a modest antiproliferative activity against human colorectal cancer cell lines HT-29. Finally, in silico molecular docking studies revealed DHFR and DNA gyrase B as potential anti-bacterial targets and in silico predictions of ADME suggested adequate drug-likeness profiles for the synthetized triarylmethanes.
- Abdmouleh, Fatma,Ali, Mamdouh Ben,Arbi, Mehdi El,Ferroud, Clotilde,Goya-Jorge, Elizabeth,Guenineche, Léna,Lagarde, Nathalie,Liagre, Bertrand,Martin, Frédérique,Ricco, Christophe,Riccobono, Charlotte,Veitía, Maité Sylla-Iyarreta
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supporting information
(2020/01/31)
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- PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
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Page/Page column 105; 106
(2019/11/12)
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- BI-FUNCTIONAL MOLECULES TO DEGRADE CIRCULATING PROTEINS
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The present invention is directed to bi-functional compounds which find use as pharmaceutical agents in the treatment of disease states and/or conditions which are through.macrophage migration inhibitory factor (MIF) or immunoglubin G (IgG). The present invention is also directed to pharmaceutical compositions which comprise these bi- functional compounds as well as methods for treating disease states and/or conditions which are mediated through MIF/lgG or where MIF/lgG is a contributing factor to the development and perpetuation of diseases and/or conditions, especially including autoimmune diseases and cancer, among others. The purpose of the present invention is to provide a molecular strategy to lower plasma MIF/lgG level in patients with autoimmune diseases or certain types of cancers. The b.i -functional molecule construct is comprised of a MIF/IgQ-targeting motif, that is derived from small molecule MIF/lgG ligands, and an ASGPr- targeting motif that binds to hepatocyte asialoglycoprotein receptor { ASGPr). The compounds selectively bind MIF or IgG in plasma and subsequently engage the endo-lysosomal pathway of hepatocytes through ASGPr. As a consequence, MIF/igG is internalized and degraded by hepatocytes, thus resulting in potential attenuation of corresponding disease symptoms which are modulated through MIF/igG.
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Page/Page column 84
(2019/11/04)
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- Naphthalimide/benzimide-based excited-state intramolecular proton transfer active luminogens: Aggregation-induced enhanced emission and potential for chemical modification
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Fluorescent organic particles are important in a number of areas, including medical imaging; hence, the development of organic materials that exhibit aggregation-induced emissions is an important objective. To that end, we report the synthesis of naphthalimide- and benzimide-based 2-(2-hydroxyphenyl)benzothiazole (HBT) derivatives (HNIBT and HPIBT, respectively) that exhibit aggregation-induced emission enhancement (AIEE), in contrast to most naphthalimide- or benzimide-based derivatives that are prone to aggregation-induced quenching. Experimental studies like single-crystal X-ray diffraction analysis and theoretical calculations demonstrate that the ability to undergo excited-state intramolecular proton transfer is pivotal for AIEE. Further studies revealed that a terminal alkynyl chain at the N-imide site of HPIBT has little impact on the emission behavior of the resultant compound (HPIBT-yl). HPIBT-Pe, an amphiphilic molecule obtained through the click reaction of HPIBT-yl and a tetraethylene-glycol-derived azide, self-assembled to form highly photostable particles that have long-term fluorescence imaging potential in cellular environments.
- Wang, Rong,Ding, Ju,Zhang, Yanrong
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p. 9152 - 9161
(2019/06/17)
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- Set of Highly Stable Amine- and Carboxylate-Terminated Dendronized Au Nanoparticles with Dense Coating and Nontoxic Mixed-Dendronized Form
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The synthesis of a novel poly(propyleneimine) (PPI) dendron in gram scale as well as its use in the formation of a highly stable, dendronized gold nanoparticle (AuNP)-based drug delivery platform is described herein. The AuNP-based platform is composed of three complementary parts: (i) a 15 nm AuNP core, (ii) a heterofunctional thioctic acid-terminated tetraethylene glycol spacer, and (iii) a third-generation PPI dendron with a unique protonation profile and diverse end-group functionalization that allows for further derivatization. The prepared dendronized AuNPs are able to withstand several rounds of lyophilization cycles with no sign of aggregation, are stable in phosphate-buffered saline and Hanks' buffer as well as in serum, and are resistant to degradation by glutathione exchange reactions. This nanocarrier platform displays a dense coating, with >1400 dendrons/AuNPs, which will enable very high payload. Furthermore, while amine-terminated AuNPs expectedly showed cytotoxicity against the MCF-7 breast cancer cell line from a NP concentration of 1 nM, the mixed monolayer AuNPs (coated with 40/60 amine/carboxylate dendrons) interestingly did not exhibit any sign of toxicity at concentrations as high as 15 nM, similar to the carboxylate-terminated AuNPs. The described dendronized AuNPs address the current practical need for a stable NP-based drug delivery platform which is scalable and easily conjugable, has long-term stability in solution, and can be conveniently formulated as a powder and redispersed in desired buffer or serum.
- Saha Ray, Arunendra,Ghann, William E.,Tsoi, Phoebe S.,Szychowski, Brian,Dockery, Lance T.,Pak, Yewon J.,Li, Wenjing,Kane, Maureen A.,Swaan, Peter,Daniel, Marie-Christine
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p. 3391 - 3403
(2019/03/07)
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- GALNAC DERIVATIVES
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Modified oligonucleotides comprising a GalNAc moiety of the present disclosure along with methods of making and use, e.g., against HBV are disclosed.
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Paragraph 0124
(2019/04/11)
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- Donor–Acceptor [2]- and [3]Catenanes Assembled from Versatile Pre-Organized Cp*Rh/Ir-Directed Pseudorotaxane Tectons
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A stepwise self-assembly protocol has been used to synthesize [2]- and [3]catenanes. Firstly, binuclear Cp*Rh/Ir-directed (Cp=pentamethylcyclopentadienyl) pseudorotaxanes were prepared through self-assembly, driven by donor–acceptor interactions between e
- Jin, Guo-Xin,Lin, Yue-Jian,Liu, Dong,Lu, Ye
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supporting information
p. 14785 - 14789
(2019/11/13)
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- Efficient Light-Harvesting Systems with Tunable Emission through Controlled Precipitation in Confined Nanospace
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Light harvesting is a key step in photosynthesis but creation of synthetic light-harvesting systems (LHSs) with high efficiencies has been challenging. When donor and acceptor dyes with aggregation-induced emission were trapped within the interior of cross-linked reverse vesicles, LHSs were obtained readily through spontaneous hydrophobically driven aggregation of the dyes in water. Aggregation in the confined nanospace was critical to the energy transfer and the light-harvesting efficiency. The efficiency of the excitation energy transfer (EET) reached 95 % at a donor/acceptor ratio of 100:1 and the energy transfer was clearly visible even at a donor/acceptor ratio of 10 000:1. Multicolor emission was achieved simply by tuning the donor/acceptor feed ratio in the preparation and the quantum yield of white light emission from the system was 0.38, the highest reported for organic materials in water to date.
- Li, Chuanqi,Zhang, Jing,Zhang, Shiyong,Zhao, Yan
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supporting information
p. 1643 - 1647
(2019/01/04)
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- METHODS FOR TREATING HEPATITIS B INFECTIONS
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Certain embodiments of the invention provide a method for identifying a patient that has a higher likelihood of responding to an HBV antigen inhibitor, such a method comprising detecting a hepatitis B virus (HBV) infected patient's genotype at one or more of the IL28B/A associated SNPs described herein, wherein the relevant genotype(s) described herein are indicative of a patient that has a higher likelihood of responding to an HBV antigen inhibitor as compared to an HBV infected patient having different genotypes at these locations.
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Page/Page column 165-167
(2019/04/09)
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- TRIPODAL SQUARAMIDE-BASED MONOMERS
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The present invention relates to a tripodal squaramide-based monomer based monomer according to formula (I) for the formation of supramolecular polymers: wherein T represents a central atom; n is an integer of from 4 to 12; and R1 is a group ac
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Page/Page column 39-41; 54; 55
(2019/09/04)
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- A novel tumor and mitochondria dual-targeted photosensitizer showing ultra-efficient photodynamic anticancer activities
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We designed and synthesized a simple, but highly effective photosensitizer (G-Mito-Pc), which can precisely target the mitochondria of epidermal growth factor receptor (EGFR)-overexpressing cancer cells, to achieve dual targeting function at both cell and
- Zhao, Xuan,Huang, Yuchao,Yuan, Gankun,Zuo, Ke,Huang, Yafan,Chen, Juanjuan,Li, Jinyu,Xue, Jinping
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supporting information
p. 866 - 869
(2019/01/21)
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- Compound for targeted ubiquitin degradation of EGFR protein as well as pharmaceutical composition and application thereof
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The invention discloses a compound for targeted ubiquitin degradation of EGFR protein or a pharmaceutically acceptable salt thereof, and also discloses a pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt thereof and
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Paragraph 0043; 0051-0053
(2019/07/04)
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- Compound for targeting decomposition of EGFR proteins and preparing method and application of compound
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The invention discloses a compound for targeting decomposition of EGFR proteins with a structure shown in a formula or a pharmaceutically acceptable salt of the compound. In the formula, R representsC1-C6 alkyl groups, m is an integer of 1-7, and n is an integer of 1-6. The invention further discloses a preparing method of the compound, a drug composition comprising the compound or the pharmaceutically acceptable salt of the compound and a pharmaceutically acceptable carrier and a preparation prepared from the drug composition. The compound shows an excellent EGFR degradation effect and goodanti-tumor activity. Therefore, the invention further discloses application of the compound in preparing drugs for preventing or/and treating cancers. The compound has a huge application prospect in the field of medical treatment.
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Paragraph 0044-0045; 0052-0054
(2019/10/01)
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- COMPOSITIONS AND METHODS CONCERNING IMMUNE TOLERANCE
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The present disclosure provides compositions comprising mannose-fused antigens to target mannose receptors. The compositions may be used to prevent immunity or reduce an immune response protein-based drugs that would otherwise elicit an immune response.
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Paragraph 0226
(2019/11/28)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 2120; 2121
(2019/07/10)
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- Dynamic host-guest interaction enables autonomous single molecule blinking and super-resolution imaging
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Synthetic host-guest complexes are inherently dynamic as they employ weak and reversible noncovalent interactions for their recognition processes. We strategically exploited dynamic supramolecular recognition between fluorescently labeled guest molecules to complementary cucurbit[7]uril hosts to obtain stochastic switching between fluorescence ON- and OFF-states, enabling PAINT-based nanoscopic imaging in cells and tissues.
- Sasmal, Ranjan,Das Saha, Nilanjana,Schueder, Florian,Joshi, Divyesh,Sheeba, Vasu,Jungmann, Ralf,Agasti, Sarit S.
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supporting information
p. 14430 - 14433
(2019/12/09)
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- Method for covalently immobilizing bioactive factor by material surface/interface photo-produced aldehyde/ketone group
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The invention relates to a method for immobilizing a bioactive factor by a material surface/interface photo-produced aldehyde/ketone group in a controllable mode. The method is characterized in that ato-be-immobilized bioactive factor does not need extra
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Paragraph 0136; 0139; 0140
(2018/11/22)
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- BIFUNCTIONAL ANTIFUNGAL AGENTS AND METHODS OF TREATING FUNGAL INFECTION
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The present invention is directed to bifunctional compounds which are useful in the treatment of fungal infections. The present compounds contains at least one fungal binding moiety (FBM) which is linked to at least one antibody binding moiety (ΑB/s
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Page/Page column 44-45
(2018/03/09)
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- HETEROBIFUNCTIONAL LINKER
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The present disclosure relates generally to heterobifunctional linkers.
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Paragraph 0174
(2018/04/20)
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- N-Heterocyclic Carbene-Modified Au–Pd Alloy Nanoparticles and Their Application as Biomimetic and Heterogeneous Catalysts
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The preparation of water-soluble, N-heterocyclic-carbene-stabilized Au–Pd alloy nanoparticles by a straightforward ligand exchange process is presented. Extensive analysis revealed excellent size retention and stability over years in water. The alloy nanoparticles were applied as biomimetic catalysts for aerobic oxidation of d-glucose, for which monometallic Au and Pd nanoparticles showed no or negligible activity. The alloy nanoparticles were further applied as titania-supported heterogeneous catalysts for the mild hydrogenation of nitroarenes and the semihydrogenation of 1,2-diphenylacetylene with a solvent-dependent selectivity switch between E- and Z-stilbene.
- Tegeder, Patricia,Freitag, Matthias,Chepiga, Kathryn M.,Muratsugu, Satoshi,M?ller, Nadja,Lamping, Sebastian,Tada, Mizuki,Glorius, Frank,Ravoo, Bart Jan
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supporting information
p. 18682 - 18688
(2018/11/23)
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- Effect of dendrimer generation and aglyconic linkers on the binding properties of mannosylated dendrimers prepared by a combined convergent and onion peel approach
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An efficient study of carbohydrate-protein interactions was achieved using multivalent glycodendrimer library. Different dendrimers with varied peripheral sugar densities and linkers provided an arsenal of potential novel therapeutic agents that could be
- Sehad, Celia,Shiao, Tze Chieh,Sallam, Lamyaa M.,Azzouz, Abdelkrim,Roy, René
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- A Ratiometric Acoustogenic Probe for in Vivo Imaging of Endogenous Nitric Oxide
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Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.
- Reinhardt, Christopher J.,Zhou, Effie Y.,Jorgensen, Michael D.,Partipilo, Gina,Chan, Jefferson
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supporting information
p. 1011 - 1018
(2018/02/07)
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- Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides
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Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conf
- Perlin, Pesach,Gharakhanian, Eric G.,Deming, Timothy J.
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p. 6196 - 6199
(2018/06/18)
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- TARGETED COMPOSITIONS
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The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
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Page/Page column 85; 87
(2018/11/10)
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- Expedient synthesis of trifunctional oligoethyleneglycol-amine linkers and their use in the preparation of PEG-based branched platforms
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We designed a convergent synthesis pathway that provides access to trifunctional oligoethyleneglycol-amine (OEG-amine) linkers. By applying the reductive coupling of a primary azide to bifunctional OEG-azide precursors, the corresponding symmetrical dialkylamine bearing two homo-functional end chain groups and a central nitrogen was obtained. These building blocks bear minimal structural perturbation compared to the native OEG backbone which makes them attractive for biomedical applications. The NMR investigations of the mechanism process reveal the formation of nitrile and imine intermediates which can react with the reduced free amine form. Additionally, these trifunctional OEG-amine linkers were employed in a coupling reaction to afford branched multifunctional PEG dendrons which are molecularly defined. These discrete PEG-based dendrons (n = 16, 18 and 36) could be useful for numerous applications where multivalency is required.
- Ursuegui, Sylvain,Schneider, Jérémy P.,Imbs, Claire,Lauvoisard, Florian,Dudek, Marta,Mosser, Michel,Wagner, Alain
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supporting information
p. 8579 - 8584
(2019/01/07)
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- PYRROLOPYRIMIDINE DERIVATIVES USEFUL AS INHIBITORS OF INFLUENZA VIRUS REPLICATION
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Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient a safe and effective amount of a compound represented by any of Formulas l-lll, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a safe and effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
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Paragraph 00307
(2018/11/22)
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- ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The description relates to inhibitors of Apoptosis Proteins (TAPs) binding compounds, including Afunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
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Paragraph 00390
(2017/02/09)
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- Neutralization of Pathogenic Fungi with Small-Molecule Immunotherapeutics
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Systemic fungal infections represent an important public health concern, and new antifungal agents are highly desirable. Herein, we describe the design, synthesis, and biological evaluation of a novel class of antifungal compounds called antibody-recruiting molecules targeting fungi (ARM-Fs). Our approach relies on the use of non-peptidic small molecules, which selectively bind fungal cells and recruit endogenous antibodies to their surfaces, resulting in immune-mediated clearance. Using the opportunistic fungal pathogen Candida albicans as a model, we identified a highly specific bifunctional molecule able to mediate the engulfment and phagocytosis of C. albicans cells by human immune cells in biologically relevant functional assays. This work represents a novel therapeutic approach to treating fungal illness with significant potential to complement and/or combine with existing treatment strategies.
- Chirkin, Egor,Muthusamy, Viswanathan,Mann, Paul,Roemer, Terry,Nantermet, Philippe G.,Spiegel, David A.
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supporting information
p. 13036 - 13040
(2017/09/18)
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