Design and synthesis of a beta-strand inducer. Application to ICAM-1/LFA-1 mediated cellular adhesion.

Int J Pept Protein Res

Department of Medicinal Chemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania, USA.

Published: March 1997

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Article Abstract

The binding of lymphocyte function associated antigen (LFA-1) to intercellular adhesion molecule (ICAM-1) is responsible for several types of cellular adhesion. Amino-acid substitution mutants of ICAM-1 have established the importance of several sequences in this protein. We selected the binding region of Glu34 for further study. One published model of domain 1 placed Glu34 near the end of a beta-strand. We designed and synthesized three tripeptide derivatives centered on the Glu34 sequence and attached a platform which, through hydrogen bonds, induces a rigid beta-strand conformation. Variable temperature NMR methods coupled with NOESY 2D NMR data enabled determination of the solution conformation of these compounds.

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http://dx.doi.org/10.1111/j.1399-3011.1996.tb00803.xDOI Listing

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