Abstract
Among RGD-dependent integrins, the alpha(v)beta3 receptor has recently received increasing attention as a therapeutic target because of its critical role in tumor-induced angiogenesis and metastasis formation. Here, we describe a new peptide antagonist of alpha(v)beta3 receptor, designed on the basis of the crystal structure of integrin alpha(v)beta3 in complex with c(RGDf[NMe]V) and the NMR structure of echistatin. Cell adhesion assays have demonstrated that the peptide is a potent and selective antagonist of the alpha(v)beta3 receptor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Adhesion / drug effects
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Crystallography, X-Ray
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Drug Design
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Humans
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Integrin alphaVbeta3 / antagonists & inhibitors*
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Integrin alphaVbeta3 / biosynthesis
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Integrin alphaVbeta3 / chemistry
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Integrins / biosynthesis
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Intercellular Signaling Peptides and Proteins
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K562 Cells
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Mimicry
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Molecular Structure
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Oligopeptides / pharmacology
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / pharmacology
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Radioligand Assay
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Receptors, Vitronectin / biosynthesis
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Vitronectin / physiology
Substances
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Integrin alphaVbeta3
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Integrins
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Intercellular Signaling Peptides and Proteins
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Oligopeptides
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Peptides
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Receptors, Vitronectin
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Vitronectin
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integrin alphaVbeta5
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echistatin
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arginyl-glycyl-aspartic acid