Assembly of binding loops on aromatic templates as VCAM-1 mimetics

The design and synthesis of cyclic mimetics of VCAM-1 protein that reproduce the integrin-binding domain are presented. The unprotected peptide precursor 37-43, Thr-Gln-Ile-Asp-Ser-Pro-Leu, was grafted onto functional templates of type naphthalene, biphenyl and benzyl through the chemoselective formation of C- and N-terminal oximes resulting in a mixture of four isomeric forms due to syn-anti isomerism of the oxime bonds. Some isomers could be monitored by HPLC and identified by NMR, The molecule containing a naphthalene-derived template mas found to inhibit the VCAM-1/VLA-4 interaction more efficiently than previously reported for sulfur-bridged cyclic peptides containing similar sequences. The finding confirms the importance of incorporating conformational constraints between the terminal ends of the peptide loop 37-43 in the design of synthetic inhibitors of the VCAM-1/integrin interaction. Copyright (C) 1999 European Peptide Society and John Wiley & Sons, Ltd.

Published in:
J. Pept. Sci., 5, 7, 313-322

 Record created 2006-02-09, last modified 2018-01-27

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