Design of peptides with alpha,beta-dehydro-residues: syntheses, crystal structures and molecular conformations of two Delta Phe-Trp containing peptides

摘要

The DeltaPhe-Trp is a newly designed moiety that was found inducing a unique conformation in peptides. The peptides Boc-L-Val-DeltaPhe-L-Trp-OCH3 (I) and Boc-L-Leu-DeltaPhe-L-Trp-OCH3 (II) were synthesized by azlactone method in solution phase. The peptide (I) was crystallized from its solution in ethanol-water mixture in orthorhombic space group P2(1)2(1)2(1) with a = 10.663(3) Angstrom, b = 11.204(3) Angstrom, c = 26.516(10) Angstrom and peptide (II) was crystallized from its solution in acetone in a monoclinic space group P2(1) with a = 9.354(1)Angstrom, b = 11.218(4)Angstrom, c = 15.633(1)Angstrom and beta = 101.83(1). The structures were determined by direct methods. Peptide (I) was refined to an R value of 0.059 for 1554 observed reflections [I greater than or equal to 2sigma (I)] and peptide (II) was refined to an R value of 0.043 for 2920 observed reflections [I greater than or equal to 2sigma (1)]. The structures of peptides (I) and (II) were found to be identical. They formed an unusual type VIa beta-turn conformation which is observed for the first time with a APhe residue at (i + 2) position indicating a unique influence of DeltaPhe-Trp moiety in inducing a reproducible new structure in peptides. (C) 2003 Elsevier Science B.V. All rights reserved. [References: 11]