STEREOCHEMICAL ANALYSIS OF HIGHER ALPHA,ALPHA-DIALKYLGLYCINE CONTAINING PEPTIDES - CHARACTERIZATION OF LOCAL HELICAL CONFORMATIONS AT DIPROPYLGLYCINE RESIDUES AND OBSERVATION OF A NOVEL HYDRATED MULTIPLE BETA-TURN STRUCTURE IN CRYSTALS OF A GLYCINE-RICH PEPTIDE

The peptide Boc-Gly-Dpg-Gly-Gly-Dpg-Gly-NHMe (1) has been synthesized to examine the conformational preferences of Dpg residues in the conte xt of a poor helix promoting sequence. Single crystals of 1 were obtai ned in the space group P2(1)/c with a = 13.716(2) Angstrom, b = 12.960 (2) Angstrom, c = 22.266(4) Angstrom, and beta = 98.05(1)degrees; R = 6.3% for 3660 data with \F-0\ > 4 sigma. The molecular conformation in crystals revealed that the Gly(1)-Dpg(2) segment adopts phi, psi valu es distorted from those expected for an ideal type II' beta-turn (phi( Gly(1)) = +72.0 degrees, psi(Gly(1)) = -166.0 degrees; phi(Dpg(2)) = - 54.0 degrees, psi(Dpg(2)) = -46.0 degrees) with an inserted water mole cule between Boc-CO and Gly(3)NH. The Gly(3)-Gly(4) segment adopts phi , psi values which lie broadly in the right handed helical region (phi (Gly(3)) = -78.0 degrees, psi(Gly(3)) = -9.0 degrees; phi(Gly(4)) = -8 0.0 degrees, psi(Gly(4)) = 18.0 degrees). There is a chiral reversal a t Dpg(5) which takes up phi, psi values in the left handed helical reg ion. The Dpg(5)-Gly(6) segment closely resembles an ideal type I' beta -turn (phi(Dpg(5)) = +56.0 degrees, psi(Dpg(5)) = +32.0 degrees; phi(G ly(6)) = +85.0 degrees, psi(Gly(6)) = -3.0 degrees). Molecules of both chiral senses are found in the centrosymmetric crystal. The C-terminu s forms a hydrated Schellman motif, with water insertion into the pote ntial 6 --> 1 hydrogen bond between Gly(1)CO and Gly(6)NH. NMR studies in CDCl3 suggest substantial retention of the multiple turn conformat ion observed in crystals. In solution the observed NOEs support local helical conformation at the two Dpg residues.