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Synthesis, conformational analysis and biological activities of lanthionine analogs of a cell adhesion modulator
Author(s) -
Li Haitao,
Jiang Xiaohui,
Goodman Murray
Publication year - 2001
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.296
Subject(s) - lanthionine , chemistry , peptide , cell adhesion , stereochemistry , integrin , receptor , biochemistry , cell
Cell adhesion is critical for many biological processes, such as hemostasis, wound healing, tumor metastasis and inflammation. Integrins are important mediators of cell adhesion. The integrin α 4 β 1 , also known as VLA‐4, is a cell surface receptor involved in inflammation. A cyclic peptide, 1‐FCA‐Arg‐c[Cys‐Asp‐Thz‐Cys]‐OH, is a potent antagonist to VLA‐4 with an IC 50 of 2.4 n. In the current study, we synthesized the lanthionine analogs of 1‐FCA‐Arg‐c[Cys‐Asp‐Thz‐Cys]‐OH and determined the conformations of both the parent compound and its lanthionine analog in solution by NMR and computer simulations. The lanthionine analog retains its selectivity to VLA‐4 with high nanomolar potency. Both molecules adopt similar topological arrangements in their conformations, while some important differences remain in the sulfur bridge region, which may cause the difference in potency. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.