Lei Wang, S. Broussy, N. Gagey-Eilstein, M. Reille‐Seroussi, F. Huguenot, M. Vidal, Wang-Qing Liu
{"title":"Inhibition of VEGF/VEGFR1 interaction by a series of C-terminal modified cyclic peptides","authors":"Lei Wang, S. Broussy, N. Gagey-Eilstein, M. Reille‐Seroussi, F. Huguenot, M. Vidal, Wang-Qing Liu","doi":"10.14800/RCI.534","DOIUrl":null,"url":null,"abstract":"Inhibition of the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) is a validated therapeutic strategy of anti-cancer treatment. This approach consists in indirect blockage of the kinase activity on VEGFR with inhibitors of protein-protein interactions, which showed great interests in oncology. The FDA approved anti-cancer agents bevacizumab (Avastin®) and ziv-aflibercept (Zaltrap®) bind specifically to VEGF are from anti-VEGF strategy. The very recently approved agent ramucirumab (Cyramza®), a recombinant humanized monoclonal antibody that specifically binds to VEGFR2 is from anti-VEGFR strategy. Based on a cyclic peptide antagonist of VEGFR1 designed from VEGF fragments, we developed, by a new synthesis process, a series of C-terminal modified cyclic peptides to improve their receptor binding ability. Three of such peptides with aromatic groups showed greatly increased VEGFR1 binding affinity in a competition ELISA-based test. This research highlight discusses the processing and findings of the recent study.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"24 1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2015-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Receptors and clinical investigation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14800/RCI.534","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Inhibition of the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) is a validated therapeutic strategy of anti-cancer treatment. This approach consists in indirect blockage of the kinase activity on VEGFR with inhibitors of protein-protein interactions, which showed great interests in oncology. The FDA approved anti-cancer agents bevacizumab (Avastin®) and ziv-aflibercept (Zaltrap®) bind specifically to VEGF are from anti-VEGF strategy. The very recently approved agent ramucirumab (Cyramza®), a recombinant humanized monoclonal antibody that specifically binds to VEGFR2 is from anti-VEGFR strategy. Based on a cyclic peptide antagonist of VEGFR1 designed from VEGF fragments, we developed, by a new synthesis process, a series of C-terminal modified cyclic peptides to improve their receptor binding ability. Three of such peptides with aromatic groups showed greatly increased VEGFR1 binding affinity in a competition ELISA-based test. This research highlight discusses the processing and findings of the recent study.