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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Discovery of pan-VEGF inhibitory peptides directed to the extracellular ligand-binding domains of the VEGF receptors

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Author(s):
Michaloski, Jussara S. [1] ; Redondo, Alexandre R. [1] ; Magalhaes, Leila S. [1] ; Cambui, Caio C. [1] ; Giordano, Ricardo J. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, POB 26077, BR-05513970 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: SCIENCE ADVANCES; v. 2, n. 10 OCT 2016.
Web of Science Citations: 3
Abstract

Receptor tyrosine kinases (RTKs) are key molecules in numerous cellular processes, the inhibitors of which play an important role in the clinic. Among them are the vascular endothelial growth factor (VEGF) family members and their receptors (VEGFR), which are essential in the formation of new blood vessels by angiogenesis. Anti-VEGF therapy has already shown promising results in oncology and ophthalmology, but one of the challenges in the field is the design of specific small-molecule inhibitors for these receptors. We show the identification and characterization of small 6-mer peptides that target the extracellular ligand-binding domain of all three VEGF receptors. These peptides specifically prevent the binding of VEGF family members to all three receptors and downstream signaling but do not affect other angiogenic RTKs and their ligands. One of the selected peptides was also very effective at preventing pathological angiogenesis in a mouse model of retinopathy, normalizing the vasculature to levels similar to those of a normal developing retina. Collectively, our results suggest that these peptides are pan-VEGF inhibitors directed at a common binding pocket shared by all three VEGFRs. These peptides and the druggable binding site they target might be important for the development of novel and selective small-molecule, extracellular ligand-binding inhibitors of RTKs (eTKIs) for angiogenic-dependent diseases. (AU)

FAPESP's process: 09/54844-0 - Identification of retinal angiogenesis molecular markers
Grantee:Jussara Michaloski Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral