6533b832fe1ef96bd129a3c8

RESEARCH PRODUCT

Thiocarbamate-Linked Polysulfonate–Peptide Conjugates As Selective Hepatocyte Growth Factor Receptor Binders

Patricia MelnykOleg MelnykOleg MelnykOleg MelnykAnthony RomieuAnthony RomieuHervé DrobecqHervé DrobecqHervé DrobecqFatima DahmaniFatima DahmaniFatima DahmaniRémi DesmetRémi DesmetRémi DesmetJérôme VicogneJérôme VicogneJérôme VicogneVéronique FafeurVéronique FafeurVéronique FafeurSoizic BesretSoizic BesretSoizic Besret

subject

DendrimersBiomedical EngineeringPharmaceutical ScienceBioengineeringPeptidemacromolecular substancesPlasma protein bindingArticleReceptor tyrosine kinaseSubstrate SpecificityStructure-Activity RelationshipThiocarbamatesmedicineHumansStructure–activity relationshipPharmacologychemistry.chemical_classificationDose-Response Relationship DrugMolecular StructurebiologyHepatocyte Growth FactorChemistryOrganic Chemistrytechnology industry and agricultureProto-Oncogene Proteins c-metProtein Structure TertiaryThiocarbamateBiochemistryHepatocyte Growth Factor ReceptorProto-Oncogene Proteins c-metbiology.proteinHepatocyte growth factorSulfonic AcidsPeptidesProtein BindingBiotechnologymedicine.drug

description

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.

yearjournalcountryeditionlanguage
2014-04-23Bioconjugate Chemistry
https://doi.org/10.1021/bc500137j