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Sequence Recognition of α ‐LFA‐1‐derived Peptides by ICAM‐1 Cell Receptors: Inhibitors of T‐cell Adhesion
Author(s) -
YusufMakagiansar Helena,
Yakovleva Tatyana V.,
Tejo Bimo A.,
Jones Karen,
Hu Yongbo,
Verkhivker Gennady M.,
Audus Kenneth L.,
Siahaan Teruna J.
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00549.x
Subject(s) - cell adhesion , cell adhesion molecule , intercellular adhesion molecule 1 , intercellular adhesion molecule , peptide , adhesion , intracellular , chemistry , receptor , microbiology and biotechnology , neural cell adhesion molecule , icam 1 , biochemistry , cell , biology , organic chemistry
Blocking the T‐cell adhesion signal from intercellular adhesion molecule‐1/leukocyte function‐associated antigen‐1 interactions (Signal‐2) can suppress the progression of autoimmune diseases (i.e. type‐1 diabetes, psoriasis) and prevent allograph rejection. In this study, we determined the active region(s) of cLAB.L peptide [cyclo(1,12)Pen‐ITDGEATDSGC] by synthesizing and evaluating the biologic activity of hexapeptides in inhibiting T‐cell adhesion. A new heterotypic T‐cell adhesion assay was also developed to provide a model for the T‐cell adhesion process during lung inflammation. Two hexapeptides, ITDGEA and DGEATD, were found to be more active than the other linear hexapeptides. The cyclic derivative of ITDGEA [i.e. cyclo(1,6)ITDGEA] has similar activity than the parent linear peptide and has lower activity than cLAB.L peptide. Computational‐binding experiments were carried out to explain the possible mechanism of binding of these peptides to intercellular adhesion molecule‐1. Both ITDGEA and DGEATD bind the same site on intercellular adhesion molecule‐1 and they interact with the Gln34 and Gln73 residues on D1 of intercellular adhesion molecule‐1. In the future, more potent derivatives of cyclo(1,6)ITDGEA will be designed by utilizing structural and binding studies of the peptide to intercellular adhesion molecule‐1. The heterotypic T‐cell adhesion to Calu‐3 will also be used as another assay to evaluate the selectivity of the designed peptides.