排序方式: 共有115条查询结果,搜索用时 15 毫秒
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Dr. Adina Borbély Dr. Fabien Thoreau Dr. Eduard Figueras Malika Kadri Dr. Jean-Luc Coll Dr. Didier Boturyn Prof. Dr. Norbert Sewald 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(12):2602-2605
The effective delivery of cytotoxic agents to tumor cells is a key challenge in anticancer therapy. Multivalent integrinspecific ligands are considered a promising tool to increase the binding affinity, selectivity, and internalization efficiency of small-molecule drug conjugates. Herein, we report the synthesis and biological evaluation of a multimeric conjugate containing the high-affinity integrin αvβ3 binding ligand RAFT-c(RGDfK)4, a lysosomally cleavable Val-Cit linker, and cryptophycin-55 glycinate, a potent inhibitor of tubulin polymerization. In vitro cytotoxicity assays verified that the multimeric RGD-cryptophycin conjugate displays improved potency compared to the monomeric analogue in integrin αvβ3 overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line. 相似文献
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Dr. David C. Kennedy Dan Grünstein Dr. Chian‐Hui Lai Prof. Dr. Peter H. Seeberger 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(12):3794-3800
Carbohydrates on cell surfaces are critical components of the extracellular landscape and contribute to cell signalling, motility, adhesion and recognition. Multivalent effects are essential to these interactions that are inherently weak. Carbohydrate‐functionalised surfaces meet an important need for studying the multivalent interactions between carbohydrates and other biomolecules. Innovations in nanomaterials are revolutionising how these carbohydrate interfaces are studied and underscore their importance in the cosmos of biochemical interactions. 相似文献
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Dr. Giuseppe Lamanna Dr. Cristian R. Smulski Neila Chekkat Dr. Karine Estieu‐Gionnet Dr. Gilles Guichard Prof. Sylvie Fournel Dr. Alberto Bianco 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(5):1762-1768
We have developed a straightforward strategy to multimerize an apoptogenic peptide that mimics the natural tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) by using adamantane‐based dendrons as multivalent scaffolds. The selective binding affinity of the ligands to TRAIL receptor 2 (TR2) was studied by surface plasmon resonance, thus demonstrating that the trimeric and hexameric forms of the peptide exert an increased affinity of about 1500‐ and 20 000‐fold, respectively, relative to the monomer. Moreover, only the trimeric and hexameric ligands were able to induce cell death in TR2 expressing cells (BJAB), thus confirming that a multivalent form of the peptide is necessary to trigger a substantial TR2‐dependent apoptotic response in vitro. These results provide interesting insight into the multivalency effect on biological ligand/receptor interactions for future therapeutic applications. 相似文献
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Design of Monodisperse and Well‐Defined Polypeptide‐Based Polyvalent Inhibitors of Anthrax Toxin 下载免费PDF全文
Sanket Patke Mohan Boggara Ronak Maheshwari Sunit K. Srivastava Manish Arha Marc Douaisi Jacob T. Martin Ian B. Harvey Matthew Brier Tania Rosen Jeremy Mogridge Prof. Ravi S. Kane 《Angewandte Chemie (International ed. in English)》2014,53(31):8037-8040
The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure–activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide‐based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin‐binding peptide were separated by flexible peptide linkers. By tuning the valency and linker length, we designed polyvalent inhibitors that were over four orders of magnitude more potent than the corresponding monovalent ligands. This strategy for the rational design of monodisperse polyvalent molecules may not only be broadly applicable for the inhibition of toxins and pathogens, but also for controlling the nanoscale organization of cellular receptors to regulate signaling and the fate of stem cells. 相似文献
25.
Multivalency by Self‐Assembly: Binding of Concanavalin A to Metallosupramolecular Architectures Decorated with Multiple Carbohydrate Groups 下载免费PDF全文
Dr. Michał J. Chmielewski Prof. Eric Buhler Dr. Jean Candau Prof. Jean‐Marie Lehn 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(23):6960-6977
Multiplication of functional units through self‐assembly is a powerful way to new properties and functions. In particular, self‐organization of components decorated with recognition groups leads to multivalent entities, amenable to strong and selective binding with multivalent targets, such as protein receptors. Here we describe an efficient, supramolecular, one‐pot valency multiplication process proceeding through self‐organization of monovalent components into well‐defined, grid‐shaped [2×2] tetranuclear complexes bearing eight sugar residues for multivalent interaction with the tetrameric lectin, concanavalin A (Con A). The grids are stable in water under physiological pH at a relatively high concentration, but dissociate readily at slightly more acidic pH or upon dilution below a certain threshold, in a type of on–off behavior. The carbohydrate‐decorated grids interact strongly and selectively with Con A forming triply supramolecular bio‐hybrid polymeric networks, which lead to a highly specific phase‐separation and quasi‐quantitative precipitation of Con A out of solution. Dramatic effects of valency number on agglutination properties were demonstrated by comparison of grids with divalent carbohydrates of covalent and non‐covalent (L ‐shaped, mononuclear zinc complex) scaffolds. The results presented here provide prototypical illustration of the power of multivalency generation by self‐assembly leading to defined arrays of functional groups and binding patterns. 相似文献
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Olga Martínez‐Ávila Dr. Karolin Hijazi Dr. Marco Marradi Dr. Caroline Clavel Dr. Colin Campion Dr. Charles Kelly Prof. Soledad Penadés Prof. Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(38):9874-9888
The HIV envelope glycoprotein gp120 takes advantage of the high‐mannose clusters on its surface to target the C‐type lectin dendritic cell‐specific intracellular adhesion molecule‐3‐grabbing non‐integrin (DC‐SIGN) on dendritic cells. Mimicking the cluster presentation of oligomannosides on the virus surface is a strategy for designing carbohydrate‐based antiviral agents. Bio‐inspired by the cluster presentation of gp120, we have designed and prepared a small library of multivalent water‐soluble gold glyconanoparticles (manno‐GNPs) presenting truncated (oligo)mannosides of the high‐mannose undecasaccharide Man9GlcNAc2 and have tested them as inhibitors of DC‐SIGN binding to gp120. These glyconanoparticles are ligands for DC‐SIGN, which also interacts in the early steps of infection with a large number of pathogens through specific recognition of associated glycans. (Oligo)mannosides endowed with different spacers ending in thiol groups, which enable attachment of the glycoconjugates to the gold surface, have been prepared. manno‐GNPs with different spacers and variable density of mannose (oligo)saccharides have been obtained and characterized. Surface plasmon resonance (SPR) experiments with selected manno‐GNPs have been performed to study their inhibition potency towards DC‐SIGN binding to gp120. The tested manno‐GNPs completely inhibit the binding from the micro‐ to the nanomolar range, while the corresponding monovalent mannosides require millimolar concentrations. manno‐GNPs containing the disaccharide Manα1‐2Manα are the best inhibitors, showing more than 20 000‐fold increased activity (100 % inhibition at 115 nM ) compared to the corresponding monomeric disaccharide (100 % inhibition at 2.2 mM ). Furthermore, increasing the density of dimannoside on the gold platform from 50 to 100 % does not improve the level of inhibition. 相似文献
27.
Inside Cover: Efficient Self‐Assembly of Di‐, Tri‐, Tetra‐, and Hexavalent Hosts with Predefined Geometries for the Investigation of Multivalency (Chem. Eur. J. 37/2015) 下载免费PDF全文
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Facile Self‐Assembly of Metallo‐Supramolecular Ring‐in‐Ring and Spiderweb Structures Using Multivalent Terpyridine Ligands 下载免费PDF全文
Jun‐Hao Fu Yin‐Hsuan Lee Yun‐Jui He Prof. Dr. Yi‐Tsu Chan 《Angewandte Chemie (International ed. in English)》2015,54(21):6231-6235
A series of metallo‐supramolecular ring‐in‐ring structures was generated by assembling CdII ions and the multivalent terpyridine ligands ( L1‐3 ) composed of one 60°‐bent and two 120°‐bent bis(terpyridine)s with varying alkyl linker lengths. The mechanistic study for the self‐assembly process excluded an entropically templated pathway and showed that the intramolecularly complexed species is the key intermediate leading to ring‐in‐ring formation. The next‐generation superstructure, a spiderweb, was produced in quantitative yield using the elongated decakis(terpyridine) ligand ( L5 ). 相似文献
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Dr. Sabrina Lusvarghi Dr. Rodolfo Ghirlando Prof. Dr. Chi‐Huey Wong Dr. Carole A. Bewley 《Angewandte Chemie (International ed. in English)》2015,54(19):5603-5608
High‐mannose‐type glycans (HMTGs) decorating viral spike proteins are targets for virus neutralization. For carbohydrate‐binding proteins, multivalency is important for high avidity binding and potent inhibition. To define the chemical determinants controlling multivalent interactions we designed glycopeptide HMTG mimetics with systematically varied mannose valency and spacing. Using the potent antiviral lectin griffithsin (GRFT) as a model, we identified by NMR spectroscopy, SPR, analytical ultracentrifugation, and microcalorimetry glycopeptides that fully recapitulate the specificity and kinetics of binding to Man9GlcNAc2Asn and a synthetic nonamannoside. We find that mannose spacing and valency dictate whether glycopeptides engage GRFT in a face‐to‐face or an intermolecular binding mode. Surprisingly, although face‐to‐face interactions are of higher affinity, intermolecular interactions are longer lived. These findings yield key insights into mechanisms involved in glycan‐mediated viral inhibition. 相似文献