Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment

Molecules

Beatriz Balsera¹  Rosario González-Muñiz¹  María Jesús Pérez de Vega¹  M. Ángeles Bonache¹  Nathalie Gagey-Eilstein²  Marie Reille-Seroussi²  Michel Vidal² 

[1] Instituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, Spain;UMR 8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, 4 avenue de l’Observatoire, Paris 75006, France;

关键词: peptides;    α-helix;    protein–protein interactions;    VEGF-VEGFR1;    angiogenesis;   

DOI  :  10.3390/molecules22111846

来源: DOAJ

【 摘 要 】

The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX5ARNX9AAX12N-NH2), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein–protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F, W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC50 value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy.

【 授权许可】

Unknown