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

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.