Novel and selective alpha(v)beta3 receptor peptide antagonist: design, synthesis, and biological behavior.
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.
Del Gatto
Annarita
A
Institute of Biostructures and Bioimaging, CNR, Department of Biological Sciences, University of Naples Federico II, and C. I. R. Pe. B., via Mezzocannone 16, 80134 Naples, Italy.
Zaccaro
Laura
L
Grieco
Paolo
P
Novellino
Ettore
E
Zannetti
Antonella
A
Del Vecchio
Silvana
S
Iommelli
Francesca
F
Salvatore
Marco
M
Pedone
Carlo
C
Saviano
Michele
M
D002448:Cell Adhesion / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D016023:Integrins / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011869:Radioligand Assay; D019030:Receptors, Vitronectin / Q000096:biosynthesis; D019096:Vitronectin / Q000502:physiology
D039302:Integrin alphaVbeta3; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid