A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site.

A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site. Research Abstract Details 

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A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site. Abstract Text:

Antagonists of VEGF-mediated angiogenesis are of great interest clinically for the treatment of solid tumors and certain forms of macular degeneration. We recently described a novel peptoid antagonist of VEGF Receptor 2 (VEGFR2) that binds to the extracellular domain of the receptor and inhibits VEGF-mediated autophosphorylation and subsequent downstream signaling. Given the structural similarities between peptides and peptoids, an obvious model for the mode of action of the peptoid is that it competes with VEGF for binding to VEGFR2. However, we present evidence here that this is not the case and that VEGF and the peptoid antagonist recognize non-overlapping surfaces located within the first three immunoglobulin-like subdomains of the receptor. These data argue that the peptoid inhibits receptor-mediated autophosphorylation by a novel allosteric mechanism that may prevent the receptor from acquiring the conformation necessary to propagate downstream signals.

A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site. Publishing Authors By Initials

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A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Bioorganic & medicinal chemistry

VOLUME: 16

Page Numbers: 6338-43

Journal Abbreviation: Bioorg. Med. Chem.

ISSN: 1464-3391

DAY: 9

MONTH: 05

YEAR: 2008

A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site. Information

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LANGUAGE: eng

NlmUniqueID: 9413298

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Grant and Affiliation Information for A peptoid antagonist of VEGF receptor 2 recognizes a 'hotspot' in the extracellular domain distinct from the hormone-binding site.

AFFILIATION: Department of Internal Medicine, Division of Translational Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9185, USA.

Country: England

AGENCY: United States NHLBI

GRANT: N01-HV-28185

ACRONYM: HV

MEDLINETA: Bioorg Med Chem

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