The pharmacophore of a peptoid VEGF receptor 2 antagonist includes both side chain and main chain residues

doi:10.1016/j.bmcl.2008.07.023

Bioorganic & Medicinal Chemistry Letters

Volume 18, Issue 22, 15 November 2008, Pages 5892-5894

https://doi.org/10.1016/j.bmcl.2008.07.023 Get rights and content

Abstract

Here we identify the pharmacophore in a peptoid that antagonizes Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) in vitro and in vivo. Only three of the side chains in the peptoid are required for activity. Surprisingly, however, main chain atoms also form critical interactions with the receptor.

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Acknowledgments

This work was supported by a contract from the National Heart, Lung, and Blood Institute (NO1-HV-28185) for the UT Southwestern Center for Proteomics Research, a grant from the Welch Foundation (I-1299), and the Effie Marie Cain Scholarship for Angiogenesis Research.

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Our first aim was to define the minimum pharmacophore responsible for the HQP09 binding activity. For that purpose, we used sarcosine scanning, a method that we have recently applied successfully to identifying the minimum pharmacophore of a peptoid antagonist of VEGFR2 (Udugamasooriya et al., 2008b). A series of sarcosine scanning derivatives was obtained by replacing one of the seven residues in HQP09 (Figure 3A, positions 1–7) with a sarcosine.
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The pharmacophore of a peptoid VEGF receptor 2 antagonist includes both side chain and main chain residues

Abstract

Graphical abstract

Section snippets

Acknowledgments

Chem. Biol.

Curr. Opin. Biotechnol.

Mol. Immunol.

Biochemistry

Chem. Commun. (Cambridge, England)

J. Am. Chem. Soc.

Endocrine Rev.