Structural basis for the interaction of a vascular endothelial growth factor mimic peptide motif and its corresponding receptors

Ricardo J. Giordano, Cristiane D. Anobom, Marina Cardó-Vila, Jorge Kalil, Ana P. Valente, Renata Pasqualini, Fabio C.L. Almeida, Wadih Arap

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is central to the survival and development of the vascular and nervous systems. We screened phage display libraries and built a peptide-based ligand-receptor map of binding sites within the VEGF family. We then validated a cyclic peptide, CPQPRPLC, as a VEGF-mimic that binds specifically to neuropilin-1 and VEGF receptor-1. Here, we use NMR spectroscopy to understand the structural basis of the interaction between our mimic peptide and the VEGF receptors. We show that: (1) CPQPRPLC has multiple interactive conformations; (2) receptor binding is mediated by the motif Arg-Pro-Leu; and (3) the Pro residue within Arg-Pro-Leu participates in binding to neuropilin-1 but not to VEGF receptor-1, perhaps representing an evolutionary gain-of-function. Therefore, Arg-Pro-Leu is a differential ligand motif to VEGF receptors and a candidate peptidomimetic lead for VEGF pathway modulation.

Original languageEnglish (US)
Pages (from-to)1075-1083
Number of pages9
JournalChemistry and Biology
Volume12
Issue number10
DOIs
StatePublished - Oct 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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