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

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/dock...

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Main Authors:	Xiaofeng Han, Yan Xu, Yilei Yang, Jingle Xi, Wang Tian, Srinivas Duggineni, Ziwei Huang, Jing An
Format:	Article
Language:	English
Published:	Public Library of Science (PLoS) 2013-01-01
Series:	PLoS ONE
Online Access:	http://europepmc.org/articles/PMC3827205?pdf=render

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spelling	doaj-bea019e1c9a34ae28a9facbf69ca43ab2020-11-24T21:45:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e8018310.1371/journal.pone.0080183Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.Xiaofeng HanYan XuYilei YangJingle XiWang TianSrinivas DuggineniZiwei HuangJing AnThe 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.http://europepmc.org/articles/PMC3827205?pdf=render
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Xiaofeng Han Yan Xu Yilei Yang Jingle Xi Wang Tian Srinivas Duggineni Ziwei Huang Jing An
spellingShingle	Xiaofeng Han Yan Xu Yilei Yang Jingle Xi Wang Tian Srinivas Duggineni Ziwei Huang Jing An Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity. PLoS ONE
author_facet	Xiaofeng Han Yan Xu Yilei Yang Jingle Xi Wang Tian Srinivas Duggineni Ziwei Huang Jing An
author_sort	Xiaofeng Han
title	Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.
title_short	Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.
title_full	Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.
title_fullStr	Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.
title_full_unstemmed	Discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the EphA4 receptor and displays anti-angiogenesis activity.
title_sort	discovery and characterization of a novel cyclic peptide that effectively inhibits ephrin binding to the epha4 receptor and displays anti-angiogenesis activity.
publisher	Public Library of Science (PLoS)
series	PLoS ONE
issn	1932-6203
publishDate	2013-01-01
description	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.
url	http://europepmc.org/articles/PMC3827205?pdf=render
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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.

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