(alphaMe)Aun: a highly lipophilic, chiral, C-alpha-tetrasubstituted alpha-amino acid. Incorporation into model peptides and preferred conformation

Using a chemo-enzymatic approach we prepared the highly lipophilic, chiral, C-alpha-methylated alpha-amino acid (alpha Me)Aun. Two series of terminally protected model peptides containing either D-(alpha Me)Aun in combination with Aib or L-(alpha Me)Aun in combination with Gly were synthesized using solution methods and fully characterized. A detailed solution conformational analysis, based on FT-IR absorption,H-1 NMR and CD techniques, allowed us to determine the preferred conformation of this amino acid and the relationship between chirality at its alpha-carbon atom and screw sense of the helix that is formed. The results obtained strongly support the view that D-(alpha Me)Aun favors the formation of the left-handed 3(10)-helical conformation.