Harnessing D-amino acids for peptide motif designs

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 type II ’ turn-3₁₀-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 3₁₀ helices. Possible origins of appreciable difference in the conformational stabilities of the diastereomers are discussed.