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Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity. | LitMetric

Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.

PLoS One

Department of Pharmacology, SUNY Upstate Medical University, Syracuse, New York, United States of America ; SUNY Upstate Cancer Research Institute, Department of Pharmacology, State University of New York, Syracuse, New York, United States of America.

Published: July 2014

AI Article Synopsis

Article Abstract

The EphA4 receptor tyrosine kinase regulates a variety of physiological and pathological processes during neural development and the formation of tumor blood vessels; thus, it represents a new and promising therapeutic target. We used a combination of phage peptide display and computer modeling/docking approaches and discovered a novel cyclic nonapeptide, now designated TYY. This peptide selectively inhibits the binding of the ephrinA5 ligand with EphA4 and significantly blocks angiogenesis in a 3D matrigel culture system. Molecular docking reveals that TYY recognizes the same binding pocket on EphA4 that the natural ephrin ligand binds to and that the Tyr3 and Tyr4 side chains of TYY are both critical for the TYY/EphA4 interaction. The discovery of TYY introduces a valuable probe of EphA4 function and a new lead for EphA4-targeted therapeutic development.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827205PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0080183PLOS

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