A NOVEL CYCLIC PENTAPEPTIDE INHIBITS ALPHA-4-BETA-1 AND ALPHA-5-BETA-1 INTEGRIN-MEDIATED CELL-ADHESION

Citation
Dm. Nowlin et al., A NOVEL CYCLIC PENTAPEPTIDE INHIBITS ALPHA-4-BETA-1 AND ALPHA-5-BETA-1 INTEGRIN-MEDIATED CELL-ADHESION, The Journal of biological chemistry, 268(27), 1993, pp. 20352-20359
Citations number
62
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
268
Issue
27
Year of publication
1993
Pages
20352 - 20359
Database
ISI
SICI code
0021-9258(1993)268:27<20352:ANCPIA>2.0.ZU;2-8
Abstract
Lymphocytes and monocytes initiate and modulate inflammatory and immun e responses for host defense. This process is dependent upon extravasa tion of leukocytes from the circulation to sites of antigenic challeng e and is controlled, in part, by various integrins, including alpha4be ta1 and alpha5beta1. A small cyclic pentapeptide that inhibits, in vit ro, both alpha4beta1 and alpha5beta1 activity is described. This pepti de, Arg-Cys-Asp-Thioproline-Cys (RCD[ThioP]C*), is cyclized by a disu lfide bond through the cysteine residues (the asterisks denote cyclizi ng residues). RCD(ThioP)C* inhibits alpha5beta1-mediated leukocyte ad hesion to the 120-kDa Arg-Gly-Asp (RGD)-containing binding site of fib ronectin. Two different adhesion activities of alpha4beta1 are also in hibited: alpha4beta1-mediated cell adhesion to the alternatively splic ed CS-1 site of fibronectin and the alpha4beta1-dependent binding of l eukocytes to cytokine-activated endothelial cells. Both alpha4beta1 an d alpha5beta1 can be purified by affinity chromatography using the imm obilized pentapeptide. The peptide does not inhibit adhesion to other extracellular matrix proteins including laminin and vitronectin. The s pecificity of the RCD(ThioP)C* peptide for alpha4beta1 and alpha5beta 1 suggests potential therapeutic utility for inhibiting inflammatory d isease.