Design of peptides with a, b-dehydro-residues: synthesis and crystal structure of a tripeptide N-benzyloxycarbonyl-DVal-DPhe-L-Ala-OCH3

In order to develop the design rules for producing specific conformations of peptides with a, b-dehydro-residues a peptide Cbz-DVal- DPhe-Ala-OCH3 was synthesized in solution phase. The crystal structure has been determined by X-ray diffraction method. The structure was refined to an R-value of 0.050. The peptide adopts a type I b-turn conformation with backbone torsion angles of two corner residues, f1ZK53.9(6)8, j1ZK33.0(6)8, f2ZK73.7(5)8 and j2ZK12.2(6)8. The conformation is stabilized by an intramolecular 4/1 hydrogen bond involving NH of Ala residue as a donor and carbonyl oxygen atom of Cbz group as an acceptor. The torsion angles, c1;1 1 Z172:8ð6Þ and c1;2 1 ZK6:9ð9Þ of DVal residue indicate that its side chain is planar while the torsion angles, c12 ZK9:0ð9Þ, c2;1 2 ZK43:4ð10Þ and c2;2 2 Z 130:1ð9Þ show that the side chain of DPhe deviates considerably from the planarity. This is the first sequence in which DVal and DPhe are introduced at adjacent positions and the structure reveals clearly that the side chain of DPhe is a relatively less rigid than that of DVal. The molecules are packed in columns parallel to c-axis. q 2004 Elsevier B.V. All rights reserved