Besret Soizic, Vicogne Jérôme, Dahmani Fatima, Fafeur Véronique, Desmet Rémi, Drobecq Hervé, Romieu Anthony, Melnyk Patricia, Melnyk Oleg
UMR CNRS 8161 , F-59021 Lille, France.
Bioconjug Chem. 2014 May 21;25(5):1000-10. doi: 10.1021/bc500137j. Epub 2014 May 5.
The capacity of many proteins to interact with natural or synthetic polyanions has been exploited for modulating their biological action. However, the polydispersity of these macromolecular polyanions as well as their poor specificity is a severe limitation to their use as drugs. An emerging trend in this field is the synthesis of homogeneous and well-defined polyanion-peptide conjugates, which act as bivalent ligands, with the peptide part bringing the selectivity of the scaffold. Alternately, this strategy can be used for improving the binding of short peptides to polyanion-binding protein targets. This work describes the design and first synthesis of homogeneous polysulfonate-peptide conjugates using thiocarbamate ligation for binding to the extracellular domain of MET tyrosine kinase receptor for hepatocyte growth factor.
许多蛋白质与天然或合成聚阴离子相互作用的能力已被用于调节其生物学作用。然而，这些大分子聚阴离子的多分散性及其较差的特异性严重限制了它们作为药物的应用。该领域的一个新兴趋势是合成均一且定义明确的聚阴离子 - 肽缀合物，其作为二价配体，肽部分赋予支架选择性。另外，该策略可用于改善短肽与聚阴离子结合蛋白靶点的结合。这项工作描述了使用硫代氨基甲酸酯连接法设计并首次合成均一的聚磺酸盐 - 肽缀合物，用于结合肝细胞生长因子的MET酪氨酸激酶受体的细胞外结构域。
