Molecular Structure of Boc-Aib-Aib-Phe-Met-NH,*DMSO. A Fragment of a Biologically Active Enkephalin Analogue

The tetra peptide t- butyloxycarbonyl- a-aminoisobutyryl- a-aminoisobutyryl- L-phenylalanyl- L-methionyl amide crystallizes in the orthorhombic space group P21212, with a = 9.096, b = 18.067, c = 21.701 A and Z = 4. The crystals contain one molecule of dimethyl sulphoxide (DMSO) associated with each peptide. The structure has been solved by direct methods and refined to an R value of 0.103 for 2 672 observed reflections. The peptide adopts a distorted 31 helical structure stabilized by two intramolecular 4-w 1 hydrogen bonds between the Boc CO and Aib(1) CO groups and the NH groups of Phe(3) and Met(4), respectively. A long hydrogen bond (N 0 = 3.35 A) is also observed between Aib(2) CO and one of the terminal amide hydrogens. The DMSO molecule is strongly hydrogen bonded to the Aib(1) NH group. The solid-state conformation agrees well with proposals made on the basis of n.m.r. studies in solution. There has been tremendous effort in attempting to establish structure-activity relationships for enkephalins and synthetic analogues.*-3 The necessity of considering both backbone conformation and side-chain 01 ientation in acyclic penta-peptide sequences contributes significantly to the complexit