Conformation of cyclo-(L-Leu-L-Tyr-δ-Avalar-δ-Avaler), a Synthetic Inhibitor of Chymotrypsin by X-Ray Analysis

Abstract

The synthetic cyclic tetrapeptide (L-Leu-L-Tyr-delta-Avaler-delta-Avaler) is an effective inhibitor of chymotrypsin, competitive with linear peptides like Ac-L-Leu-L-Tyr-OMe. An x-ray diffraction analysis of the crystal structure of the cyclic peptide shows that the conformation of the 18-membered ring is very similar to that of one of the four conformers of cyclic hexaglycyl. There is no internal hydrogen bonding. Side chains are located on two "corners" of the approximately rectangular ring. The chii1 angles for Leu and Tyr are -74 and -48 degrees, respectively. The Leu side chain is extended away from the polypeptide ring while the Tyr side chain is folded under an adjacent carbonyl bond. The cell parameters for the space group P2U are: a = 9.361 (3 A, b = 19.039 (10) A, c = 9.603 (3), A, and beta = 116.54 (3) degrees. A molecule of (CH3)2SO (disordered) and a molecule of H2O cocrystallized with the cyclic peptide.