Onset of the fully extended conformation in (alpha Me)Leu derivatives and short peptides.

The X-ray diffraction crystal structures of the (alpha Me)Leu derivative mClAc-D-(alpha Me) Leu-OH and the terminally protected tripeptide Z-D-(alpha Me) Leu-(L-Ala)2-OMe show the onset of the fully extended (C5) conformation for the (alpha Me) Leu residue in both independent molecules in the asymmetric unit of the former compound and in two out of the four independent molecules in the asymmetric unit of the latter compound. In addition, conformational analysis in CDCl3 solution (using FT-infra-red absorption and 1H nuclear magnetic resonance) revealed the occurrence of a significant population of fully extended conformers throughout the entire sequence of the (alpha Me) Leu homochiral homopeptides pBrBz-[D-(alpha Me) Leu]n-OtBu (from monomer to tetramer). Taken together, these results represent a clear indication that this peptide secondary structure, uncommon for protein amino acids and other C alpha-methylated chiral residues, is not a rare observation in (alpha Me) Leu derivatives and short peptides.