Conformational preferences of heterochiral peptides. Crystal structures of heterochiral peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala-OMe--enhanced stability of beta-sheet through C-H...O hydrogen bonds.

The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala-Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group P2(1),2(1),2(1), with a = 9.401 (4), b = 17.253 (5), c = 36.276 (9)A. V = 5,884 (3) A3, Z = 8, R = 0.086. VALa crystallises in space group P2(1) with a = 9.683 (9), b = 17.355 (7), c = 18.187 (9) A, beta = 95.84 (8) degrees , V = 3,040(4) A3, Z = 4, R = 0.125. There are two molecules in the asymmetric unit in antiparallel beta-sheet arrangement in both the structures. Several of the Calpha hydrogens are in hydrogen bonding contact with the carbonyl oxygen in the adjacent strand. An analysis of the observed conformational feature of D-chiral amino acid residues in oligopeptides, using coordinates of 123 crystal structures selected from the 1998 release of CSD has been carried out. This shows that all the residues except D-isoleucine prefer both extended and alphaL conformation though the frequence of occurence may not be equal. In addition to this, D-leucine, valine, proline and phenylalanine have assumed alphaR conformations in solid state. D-leucine has a strong preference for helical conformation in linear peptides whereas they prefer an extended conformation in cyclic peptides.

Harnessing D-amino acids for peptide motif designs. Synthesis and solution conformation of Boc-D-Glu-Ala-Gly-Lys-NHMe and Boc-L-Glu-Ala-Gly-Lys-NHMe.

In examining the use of D-amino acids in designing specific peptide folding motifs, the tetrapeptide Boc-D-Glu-Ala-Gly-Lys-NHMe 1 and its analog 2 featuring L-Glu were synthesized for a comparison of their solution conformations by NMR spectroscopy. The temperature coefficients of amide proton resonances, NOE data, side-chain CH2 anisotropies and salt titration results suggest a weak type II reverse-turn conformation for peptide 2, and a tandem II' turn-3(10)-helix conformation of appreciable conformational stability for peptide 1 in apolar solvents. The latter is of potential interest as the N-terminal helix cap that could support the design of longer 3(10) helices. Possible origins of appreciable difference in the conformational stabilities of the diastereomers are discussed.

Crystal structures of a D-residue containing tetrapeptides. 1. tert-Boc-D-valyl-alanyl-leucyl-alanyl-methoxide, butanol solvate.

The crystal structure of a heterochiral peptide, viz. Boc-D-Val-Ala-Leu-Ala-OMe, with a D-residue in the beginning of the sequence has been determined (a = 9.464(5), b = 35.615(5), c = 9.703(2) A, space group P2(1)2(1)2, Z = 4, R = 0.09). The peptide is in the extended beta-conformation and the packing is stabilised by four N--H ... O hydrogen bonds in an antiparallel beta-sheet arrangement. The solvent molecule is disordered and does not have any specific interactions with the peptide.

Crystal structures of heterochiral peptides. Part II. tert-Boc-valyl-D-alanyl-leucyl-alanyl methoxide.

Crystal structure of a heterochiral peptide, viz. Boc-Val1-D-Ala2-Leu3-Ala4-OMe with a D chiral residue in the second position of a sequence, has been determined [a = 40.44(1), b = 4.887(5), c = 15.381(5) A, beta = 109.6(1)degrees, space group C2, Z = 4, R = 0.11]. The peptide is in a parallel beta-sheet structure terminated by a distinct local bend. The structure is established by N-H...O as well as C alpha-H...O hydrogen bonds. The contiguous C alpha-H...O hydrogen bond observed in this structure is an unique observation.