101187-39-7Relevant articles and documents
Zinc(II)cyclen-peptide conjugates interacting with the weak effector binding state of Ras
Schmidt, Florian,Rosnizeck, Ina C.,Spoerner, Michael,Kalbitzer, Hans Robert,K?nig, Burkhard
, p. 38 - 48 (2011)
Zinc(II)cyclen-peptide hybrid compounds and bis-zinc(II)cyclen complexes are prepared as potential binders of the guanine nucleotide binding protein Ras, an important molecular switch in cellular signal transduction. The design of the compounds is based on the previous observation that zinc(II)cyclen complexes could serve as lead compounds for inhibitors of Ras-effector interaction and thus be able to interrupt Ras induced signal transduction. Zinc(II)cyclen selectively stabilizes conformational state 1 of active Ras, a conformational state with drastically decreased affinity to effector proteins like Raf-kinase. To achieve higher binding affinities of such Ras-Raf interaction inhibitors, zinc(II)cyclen conjugates with short peptides, derived from the sequence of the Ras-activator SOS, were prepared by solid phase synthesis protocols. Dinuclear bis-zinc(II)cyclen complexes were obtained from alkyne-azide cycloaddition reactions. NMR investigations of the prepared compounds revealed that the peptide conjugates do not lead to an increase in Ras binding affinity of the metal complex-peptide conjugates. The dinuclear zinc complexes lead to an immediate precipitation of the protein prohibiting spectroscopic investigations of their binding.
Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery
Bell, Craig A.,Blinco, James P.,Ediriweera, Gayathri R.,Fletcher, Nicholas L.,Fuchs, Adrian V.,Houston, Zachary H.,Howard, Christopher B.,Mahler, Stephen M.,Simpson, Joshua D.,Thurecht, Kristofer J.,Van De Walle, Matthias,Venkatachalam, Taracad K.
, p. 3268 - 3280 (2020)
There remain several key challenges to existing therapeutic systems for cancer therapy, such as quantitatively determining the true, tissue-specific drug release profile in vivo, as well as reducing side-effects for an increased standard of care. Hence, it is crucial to engineer new materials that allow for a better understanding of the in vivo pharmacokinetic/pharmacodynamic behaviours of therapeutics. We have expanded on recent "click-to-release" bioorthogonal pro-drug activation of antibody-drug conjugates (ADCs) to develop a modular and controlled theranostic system for quantitatively assessing site-specific drug activation and deposition from a nanocarrier molecule, by employing defined chemistries. The exploitation of quantitative imaging using positron emission tomography (PET) together with pre-targeted bioorthogonal chemistries in our system provided an effective means to assess in real-time the exact amount of active drug administered at precise sites in the animal; our methodology introduces flexibility in both the targeting and therapeutic components that is specific to nanomedicines and offers unique advantages over other technologies. In this approach, the in vivo click reaction facilitates pro-drug activation as well as provides a quantitative means to investigate the dynamic behaviour of the therapeutic agent.
Tetraethylene glycol-derived spacer for oligonucleotide synthesis
Gunzenhauser,Biala,Strazewski
, p. 1223 - 1224 (1999)
3,6,9-Trioxaundecane-1,11-diisocyanate (6) was synthesised from tetraethylene glycol in 5 steps and 48 % overall yield. Spacer 6 was monofunctionalised with the fully protected adenosyl-3'-O-succinate derivative 7 and linked to aminomethyl polystyrene affording a solid support suitable for oligoribonucleotide synthesis (loading: ~20 μmol/g). The HPLC analysis of a crude oligoribonucleotide synthesis and the yield of the full- length product show that this spacer compares well to hexamethylene diamine.
Synthesis of peptide homo- and heterodimers as potential mimics of platelet-derived growth factor BB
Stubbing, Louise A.,Kaur, Harveen,Feng, Sheryl X.,Aalderink, Miranda,Dragunow, Michael,Brimble, Margaret A.
, (2020)
Pericyte loss is correlated with blood-brain barrier leakage in neurological disorders such as Alzheimer's disease. The platelet-derived growth factor receptor β (PDGFRβ)/platelet-derived growth factor BB (PDGF-BB) signalling pathway is key to the regulation of pericyte survival and proliferation. A series of peptide dimers mimicking the ligand PDGF-BB were prepared in the hope of stimulating PDGFRβ internalisation and activation of this pathway. Copper-catalysed azide-alkyne cycloaddition of peptide monomers with PEGylated linkers of varying length afforded the desired peptide dimers. Evaluation of the peptide dimers in human brain pericyte assays revealed no effect on PDGFRβ internalisation nor cell proliferation at concentrations 10 μM. The peptide dimers also did not act as antagonists at PDGFRβ at concentrations 10 μM.
Polyacrylamide pseudo crown ethers via hydrogen bond-assisted cyclopolymerization
Kimura, Yoshihiko,Miyabara, Yuichiro,Terashima, Takaya,Sawamoto, Mitsuo
, p. 3294 - 3302 (2016)
Polyacrylamide pseudo crown ethers with large in-chain rings (15–24 membered) were synthesized by hydrogen bond-mediated cyclopolymerization of bisacrylamides comprising poly(ethylene oxide) spacers (PEGnDAAm, ethylene oxide units: n = 3–6). The monomers undergo the intramolecular hydrogen bonding of the bisacrylamide units in halogenated solvents to dynamically place the two olefins adjacently. As a result, the bisacrylamides homogeneously allowed controlled radical cyclopolymerization without any macroscopic gelation in 1,2-dichloroethane, even at relatively high concentration of monomers (200 mM), to directly provide precision cyclopolyacrylamides and the related copolymers with high cyclization efficiency (84–98%). Owing to the in-chain ring pendants, a cyclopolyacrylamide had glass transition temperature higher than a corresponding polyacrylamide with linear pendants.
Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer's Tau
El Khoury, Anton,Seidler, Paul M.,Eisenberg, David S.,Harran, Patrick G.
, p. 4263 - 4271 (2021)
The naturally occurring flavonoid ( )-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting groupfree catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer s-related tau tangles.
Cyto-mechanoresponsive polyelectrolyte multilayer films
Davila, Johanna,Chassepot, Armelle,Longo, Johan,Boulmedais, Fouzia,Reisch, Andreas,Frisch, Benoit,Meyer, Florent,Voegel, Jean-Claude,Mesini, Philippe J.,Senger, Bernard,Metz-Boutigue, Marie-Helene,Hemmerle, Joseph,Lavalle, Philippe,Schaaf, Pierre,Jierry, Loic
, p. 83 - 86 (2012)
Cell adhesion processes take place through mechanotransduction mechanisms where stretching of proteins results in biological responses. In this work, we present the first cyto-mechanoresponsive surface that mimics such behavior by becoming cell-adhesive t
Clickable iron oxide NPs based on catechol derived ligands: Synthesis and characterization
Pozo-Torres, Esther,Caro, Carlos,Avasthi, Ashish,Páez-Mu?oz, Jose María,García-Martín, María Luisa,Fernández, Inmaculada,Pernia Leal, Manuel
, p. 3257 - 3266 (2020)
Clickable magnetic nanoparticles have attracted great attention as potential nanoplatforms for biomedical applications because of the high functionalization efficiency of their surfaces with biomolecules, which facilitates their bio-compatibilization. However, the design and synthesis of clickable NPs is still challenging because of the complexity of the chemistry on the magnetic NP surface, thus robust methods that improve the ligand synthesis and the transfer of magnetic NPs in physiological media being in high-demand. In this work, we developed a versatile and enhanced synthetic route to fabricate potentially clickable IONPs of interest in nanomedicine. Catechol anchor ligands with different stereo-electronic features were synthetized from a hetero bi-functional PEG spacer backbone. The resulting catechol ligands transferred in good yields and high stability to magnetic NPs by an improved energetic ligand exchange method that combines sonication and high temperature. The azido functionalized IONPs exhibited excellent characteristics as T2 MRI contrast agents with low cytotoxicity, making these clickable magnetic NPs promising precursors for nanomedicines.
Synthesis and metal-binding properties of novel "fullerenocrowns"
Ikeda, Atsushi,Fukuhara, Chie,Shinkai, Seiji
, p. 407 - 408 (1997)
"Fullerenocrowns" in which C60 carbons are directly included as a ring member in the crown ring were synthesized for the first time; the UV-Vis absorption spectra were sensitively changed by the addition of metal and ammonium cations.
Synthesis, anti-microbial activity and molecular docking studies on triazolylcoumarin derivatives
Satheeshkumar, Chinnadurai,Ravivarma, Mahalingam,Arjun, Pandian,Silambarasan, Vaithiyanathan,Raaman, Nanjian,Velmurugan, Devadasan,Song, Changsik,Rajakumar, Perumal
, p. 565 - 571 (2015)
A series of triazolylcoumarins was synthesized by the cycloaddition of acetylenic derivatives to azide in the presence of Cu(I) catalyst at room temperature. All the synthesized compounds were evaluated for their anti-microbial activity against Gram-posit
Highly soluble electroactive ethylenedioxythiopene (EDOT)-based copolymer obtained via ‘click’ copolymerization
Kim, Hern,More, Pawan P.,Puguan, John Marc C.,Rathod, Pramod V.
, (2021)
Poly (3,4-ethylenedioxythiophene) (PEDOT), in spite of its remarkable attributes, remains insoluble in many common solvents. By adopting the copolymerization approach, a new electroactive polythiopene derivative is synthesized with enhanced solubility by polymerizing an alkyne-functionalized (3-4-ethylenedioxythiophene) (EDOT) and an azide-functionalized tetraethylene glycol via copper catalyzed alkyne-azide cycloaddition (CuAAC). The copolymer, EDOT-co-1,2,3-triazolium, exhibits an interesting chemical structure that makes it an ideal electroactive material. With its polar nature, it readily dissolves in solvents such as DMSO, DMF and PC. Furthermore, the introduction of the oxyethylene monomer as well as the formation of the 1,2,3-triazole during the polymerization step lowers its glass transition temperature inducing a faster switching between its reduced and oxidized state compared to pristine PEDOT.
The Synthesis and Biological Evaluation of Some C-9 and C-10 Substituted Derivatives of the RNA Polymerase i Transcription Inhibitor CX-5461
Amarasiri, Madushani,Vo, Yen,Gardiner, Michael G.,Poh, Perlita,Soo, Priscilla,Pavy, Megan,Hein, Nadine,Ferreira, Rita,Hannan, Katherine M.,Hannan, Ross D.,Banwell, Martin G.
, p. 540 - 556 (2021/04/23)
The regio-isomeric alkynyl-substituted derivatives, 2 and 3, of the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 (1) were prepared and the active one (compound 3) subjected to click reactions ([3 + 2]-cycloaddition reactions) with certain alkyl azides bearing biotin or fluorescent tags. Compounds 2 and 3, as well as four [3 + 2]-cycloadducts of the latter, were subjected to biological evaluation in a human acute myeloid leukemia cell line model. Among the six compounds tested only alkyne 3 remained active but this was less potent than parent 1.
Tetrahydroisoquinoline derivative as well as preparation method and medical application thereof
-
, (2021/04/21)
The invention relates to a tetrahydroisoquinoline derivative, a preparation method thereof and medical application of the tetrahydroisoquinoline derivative. Specifically, the invention relates to a tetrahydroisoquinoline derivative as shown in a general formula (I) and a medicinal salt thereof, a preparation method of the tetrahydroisoquinoline derivative and the medicinal salt thereof, and application of the tetrahydroisoquinoline derivative and the medicinal salt thereof as NHE3 inhibitors, particularly as a therapeutic agent for diseases related to body fluid retention or salt overload or gastrointestinal diseases. Wherein the definition of each substituent in the general formula (I) is the same as the definition in the specification.
