Design of peptides with alpha,beta-dehydro-residues: synthesis and crystal structure of a tripeptide N-benzyloxycarbonyl-Delta Val-Delta Phe-L-Ala-OCH3

摘要

In order to develop the design rules for producing specific conformations of peptides with alpha, beta-dehydro-residues a peptide Cbz-Delta Val-Delta Phe-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 beta-tum conformation with backbone torsion angles of two corner residues, phi(1) = -53.9(6)degrees, psi(1) = - 33.0(6)degrees, phi(2)= -73.7(5)degrees and psi(2)= - 12.2(6)degrees. 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, X-1(1,1) = 172.8(6) and X-1(1,2) = -6.9(9) of Delta Val residue indicate that its side chain is planar while the torsion angles, X-2(1) = -9.0(9), X-2(2,1),1 = -43.4(10) and X-2(2,2) 2 2 2 130.1(9) show that the side chain of Delta Phe deviates considerably from the planarity. This is the first sequence in which Delta Val and APhe are introduced at adjacent positions and the structure reveals clearly that the side chain of APhe is a relatively less rigid than that of Delta Val. The molecules are packed in columns parallel to c-axis. C 2004 Elsevier B.V. All rights reserved.