Peptide design: crystal structure of a helical peptide module attached to a potentially nonhelical amino terminal...

The peptide Boc-Gly-Dpg-Gly-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe has been designed to examine the structural consequences of placing a short segment with a low helix propensity at the amino terminus of a helical heptapeptide module. The Gly-Dpg-Gly segment is a potential connecting element in the synthetic construction of a helix-linker-helix motif. Crystal parameters for the peptide are P21, a = 8.651 (3) A, b = 46.826 (13) A, c = 16.245 A, beta = 90.13 (3) degrees, Z = 4; 2 independent molecules/asymmetric unit. The structure reveals almost identical conformations for the two independent molecules. The backbone is completely helical for residues 2-9, with on 4 --> 1 hydrogen bond and six 5 --> 1 hydrogen bonds. The alpha, alpha-di-n-propylglycine residue adopts a helica conformation. Gly (1) adopts an extended conformation resulting in a nonhelical N-terminus, with the Boc group swinging away from the helix. the lateral association of helices in the beta axis direction is unusual in that the helix axes are directed up or down (parallel or antiparallel) by pairs: decrease decrease increase increase decrease decrease, etc.