Peptide design 3(10)-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3.

Abstract

alpha,beta-Dehydroamino acids are expected to provide conformational constraint to the peptide backbone. A pentapeptide containing two dehydrophenylalanines (delta ZPhe) separated by one L-amino acid has been synthesized and its solid state conformation determined. The pentapeptide, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3, crystallizes from aqueous methanol in the orthorhombic space group P2(1)2(1)2(1). There are four formula units, C35H46N6O7, in a unit cell of dimensions a = 10.155(3), b = 15.175(1), and c = 23.447(2) A, at room temperature. The structure was solved by direct methods program, SIR88, and refined to a final R = 0.038 based on 3049 reflections with I > 2 sigma (I). All the peptide links are trans and the backbone conformation of the pentapeptide can be described as a 3(10)-helix, with mean phi,psi values of -65.1 degrees and -22.8 degrees (the value is averaged over the first four residues). There are four intramolecular 4-->1 type hydrogen bonds characteristic of 3(10)-type helices. In the crystal, the helices are held together by intermolecular N-H...O = C head-to-tail and lateral hydrogen bonding between symmetry related molecules. This mode of packing is similar to the packing motifs observed so often in other oligopeptides that adopt a 3(10)-helical structure.