Synthesis and conformational properties of a synthetic cyclic peptide for the active site of alpha-chymotrypsin.

A nonapeptide Ac-His-Phe-Gly-Cys-D-Phe-Ser-Gly-Glu-Cys-NH2 (XI) cyclized through the cysteines at positions 4 and 9 is synthesized as a model active site for the enzyme alpha-chymotrypsin. A CPK model of XI indicates that the peptide will have a high probability of folding into a conformation in which the two beta-phenyls interact to form a hydrophobic site to one side of the cyclohexyl structure, and the Ser-His-Glu side chains form a hydrogen bonded triad over the plane of cyclopeptidyl structure. Substrates can then bind at the hydrophobic pocket formed by the beta-phenyls and be acted upon by the Ser-His-Glu catalytic triad, as in the enzyme.