Comparative conformational analysis of peptides based on the two C-alpha-tetrasubstituted, C-beta-branched, chiral alpha-amino acids (alphaMe)Dip and (alphaMe)Val

For the first time a number of terminally protected model peptides (to the pentamer level) of the sterically demanding α-amino acid Cα-methyl,Cα-diphenylmethylglycine, (αMe)Dip, in combination with either Ala or Gly residues, have been synthesized (by solution methods) and fully characterized. In a parallel synthesis the corresponding peptides based on the related α-amino acid Cα-methyl,Cα-isopropylglycine, (αMe)Val, have also been prepared. The results of a comparative conformational analysis, performed by using FTIR absorption, 1H NMR, and X-ray diffraction techniques, favour the conclusion that, in contrast to the potent β-turn and 310-helix promoter (αMe)Val, (αMe)Dip may induce either a folded or a fully extended conformation. These findings indicate that, despite the common Cα-methylated and Cβ-branched features, (αMe)Dip and (αMe)Val are characterized by partially divergent conformational bias.