Linear oligopeptides .352. Synthesis, characterization and solution conformational analysis of C-alpha-methyl-homo-phenylalanine [(alpha Me)Hph] containing peptides

For the first time a number of derivatives and terminally blocked model peptides (to the pentapeptide level) of the sterically demanding C-alpha-methyl-homo-phenylalanine, (alpha Me)Hph, residue have been synthesized (by solution methods) and fully characterized. The results of a solution conformational analysis, performed by using FTIR and H-1 NMR spectroscopies, favour the conclusion that (alpha Me)Hph is as potent a beta-turn and helix promoter as (alpha Me)Phe (C-alpha-methylphenylalanine) and (alpha Et)Phe (C-alpha-ethylphenylalanine), and more potent than the Phe parent amino acid. In addition, a CD study of N-alpha-para-bromobenzoylated peptides suggests that the relationship between (alpha Me)Hph alpha-carbon chirality and the prevailing screw sense of the turn and helical structures that are formed is opposite to that found for (alpha Me)Phe and (alpha Et)Phe peptides, i.e. L-amino acids give right-handed helicities. This relationship is the same as that exhibited by protein amino acids, including Phe.