Preferred solution conformation of peptides rich in the lipophilic, chiral, C-alpha-methylated alpha-amino acid (alpha Me)Aoc

The lipophilic, chiral, Cα-methylated α-amino acid L-(αMe)Aoc (2-methyl-2-amino-octanoic acid) was prepared using a chemo-enzymatic approach. Two series of terminally protected model peptides, from dimer through to hexamer, containing L-(αMe)Aoc in combination with either Gly or Aib, were synthesized by solution methods and were fully characterized. A solution conformational analysis, based on FT-IR absorption, LH-NMR and circular dichroism (CD) techniques, was performed with the aim at determining the preferred conformation of this novel amino acid and the relationship between chirality at its α-carbon atom and screw sense of the helix that is formed. The results obtained strongly support the view that L-(αMe)Aoc favours the formation of the right-handed 310-helical conformation.