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Peptides Inhibitors of F11R/JAM‐A Adhesion Molecules
Author(s) -
Clement Cristina Corina,
Babinska Anna,
Kornecki Elizabeth,
Ehrlich Yigal H,
Philipp Manfred
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.651.7
Subject(s) - platelet , peptide , microbiology and biotechnology , platelet adhesiveness , chemistry , in vitro , receptor , cell adhesion molecule , adhesion , cancer research , medicine , pharmacology , biochemistry , biology , platelet aggregation , immunology , organic chemistry
F11‐R receptor was characterized as an adhesion protein, called also aka JAM‐A (or JAM‐1), which under normal physiological conditions is expressed constitutively on the surface of the platelets and localized within tight junctions of endothelial cells (EC). The utilization of specific F11R/JAM‐A peptide antagonists and recombinant proteins supported the role of F11R/JAM‐A in the process of platelets adhesion to inflamed endothelial cells and identified plaque formation leading to inflammatory thrombosis and atherosclerosis where the platelets have a critical influence in the progression and development of the cardiovascular disease. Thus, the development of new drugs antagonizing the F11R/JAM‐A function could evolve as an effective strategy for the treatment of atherosclerosis, heart attacks and stroke. We present one of the first trials toward development of peptide‐based inhibitors of F11R/JAM‐A function. Among many trials, the peptide D‐Lys‐Ser‐Val‐Ser‐D‐Arg‐Glu‐Asp‐Thr‐Gly‐Thr‐Tyr‐Thr‐Cys‐CONH2 proved to be a potent inhibitor of human platelets aggregation in vitro. Further molecular docking experiments showed that this peptide makes favorable hydrophobic and electrostatic interactions within the proposed binding site of JAM‐1 (X‐Ray structure 1nbq.pdb was used as template).