A novel integrin α5β1 antagonistic peptide, A5-1, screened by Protein Chip system as a potent angiogenesis inhibitor

作者: Eung-Yoon Kim , Ji Young Bang , Soo-Ik Chang , In-Cheol Kang

DOI: 10.1016/J.BBRC.2008.10.166

关键词:

摘要: Integrin alpha5beta1 immobilized on a ProteoChip was used to screen new antagonistic peptides from multiple hexapeptide sub-libraries of the positional scanning synthetic peptide combinatorial library (PS-SPCL). The integrin alpha5beta1-Fibronectin interaction demonstrated chip. A novel ligand, A5-1 (VILVLF), with high affinity identified libraries this chip-based screening method basis competitive inhibition assay. inhibits integrin-fibronectin in dose-dependent manner (IC(50); 1.56+/-0.28 microM. In addition, it human umbilical vein endothelial cell proliferation, migration, adhesion, tubular network formation, and bFGF-induced neovascularization chick chorioallantoic membrane. These results suggest that will be potent inhibitor neovascularization.

参考文章(23)
A P Mould, L A Wheldon, A Komoriya, E A Wayner, K M Yamada, M J Humphries, Affinity chromatographic isolation of the melanoma adhesion receptor for the IIICS region of fibronectin and its identification as the integrin alpha 4 beta 1. Journal of Biological Chemistry. ,vol. 265, pp. 4020- 4024 ,(1990) , 10.1016/S0021-9258(19)39696-6
Y Iwamoto, F. Robey, J Graf, M Sasaki, H. Kleinman, Y Yamada, G. Martin, YIGSR, a synthetic laminin pentapeptide, inhibits experimental metastasis formation. Science. ,vol. 238, pp. 1132- 1134 ,(1987) , 10.1126/SCIENCE.2961059
Luciana Marinelli, Axel Meyer, Dominik Heckmann, Antonio Lavecchia, Ettore Novellino, Horst Kessler, Ligand Binding Analysis for Human α5β1 Integrin: Strategies for Designing New α5β1 Integrin Antagonists Journal of Medicinal Chemistry. ,vol. 48, pp. 4204- 4207 ,(2005) , 10.1021/JM040224I
Maria Grazia Cattaneo, Sandra Pola, Pierangelo Francescato, Francesco Chillemi, Lucia Maria Vicentini, Human endostatin-derived synthetic peptides possess potent antiangiogenic properties in vitro and in vivo. Experimental Cell Research. ,vol. 283, pp. 230- 236 ,(2003) , 10.1016/S0014-4827(02)00057-5
Sergiy Sukhanov, Patrick Delafontaine, Protein chip-based microarray profiling of oxidized low density lipoprotein-treated cells Proteomics. ,vol. 5, pp. 1274- 1280 ,(2005) , 10.1002/PMIC.200400985
Peter C. Brooks, Anthony M.P. Montgomery, Mauricio Rosenfeld, Ralph A. Reisfeld, Tianhua Hu, George Klier, David A. Cheresh, Integrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels Cell. ,vol. 79, pp. 1157- 1164 ,(1994) , 10.1016/0092-8674(94)90007-8
D. Cue, S. O. Southern, P. J. Southern, J. Prabhakar, W. Lorelli, J. M. Smallheer, S. A. Mousa, P. P. Cleary, A nonpetide integrin antagonist can inhibit epithelial cell ingestion of Streptococcus pyogenes by blocking formation of integrin α5β1-fibronectin-M1 protein complexes Proceedings of the National Academy of Sciences of the United States of America. ,vol. 97, pp. 2858- 2863 ,(2000) , 10.1073/PNAS.050587897
Sheila E Francis, Keow Lin Goh, Kairbaan Hodivala-Dilke, Bernhard L Bader, Margaret Stark, Duncan Davidson, Richard O Hynes, None, Central Roles of α5β1Integrin and Fibronectin in Vascular Development in Mouse Embryos and Embryoid Bodies Arteriosclerosis, Thrombosis, and Vascular Biology. ,vol. 22, pp. 927- 933 ,(2002) , 10.1161/01.ATV.0000016045.93313.F2
Yoonsuk Lee, Eun Kyoung Lee, Yong Wan Cho, Takuya Matsui, In-Cheol Kang, Tai-Sun Kim, Moon Hi Han, ProteoChip: a highly sensitive protein microarray prepared by a novel method of protein immobilization for application of protein-protein interaction studies. Proteomics. ,vol. 3, pp. 2289- 2304 ,(2003) , 10.1002/PMIC.200300541