Inhibition of VEGF/VEGFR1 interaction by a series of C-terminal modified cyclic peptides

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.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
一系列c端修饰的环肽抑制VEGF/VEGFR1相互作用
抑制血管内皮生长因子(VEGF)及其受体(VEGFRs)之间的相互作用是一种有效的抗癌治疗策略。这种方法包括用蛋白-蛋白相互作用抑制剂间接阻断VEGFR上的激酶活性,这在肿瘤学中显示出极大的兴趣。FDA批准的抗癌药物贝伐单抗(Avastin®)和ziv-aflibercept (Zaltrap®)特异性结合VEGF是来自抗VEGF策略。最近批准的药物ramucirumab (Cyramza®)是一种重组人源化单克隆抗体,特异性结合VEGFR2,来自抗vegfr策略。我们以VEGF片段设计的VEGFR1环肽拮抗剂为基础,通过新的合成工艺,开发了一系列c端修饰的环肽,以提高其受体结合能力。在基于竞争elisa的测试中,其中三种具有芳香基团的肽显示出大大增加的VEGFR1结合亲和力。本研究重点讨论了最近研究的过程和结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
The role of leptin in the central nervous system remyelination 20 Years Anniversary for SORLA/SORL1 (1996-2016) Targeting sympathetic glia for treating cardiovascular diseases Computational analysis in Influenza virus HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1