LINEAR OLIGOPEPTIDES .275. REVERSE RELATIONSHIP BETWEEN ALPHA-CARBON CHIRALITY AND HELIX HANDEDNESS IN (ALPHA-ME)PHE PEPTIDES

The crystal-state preferred conformations of two tripeptides, one tetr apeptide, and one pentapeptide, each containing a single residue of th e chiral. C(alpha,alpha)-disubstituted glycine C(alpha)-methyl, C(alph a)-benzylglycine [(alphaMe)Phe], have been determined by X-ray diffrac tion. The tripeptides are Z-L-(alphaMe)Phe-(Aib)2-OH dihydrate and Z-A ib-D-(alphaMe)Phe-Aib-OtBu, the tetrapeptide is Z-(Aib)2-D-(alphaMe)Ph e-Aib-OtBu. and the pentapeptide is pBrBz-(Aib)2-DL-(alphaMe)Phe-(Aib) 2-OtBu. While the two tripeptides are folded in a beta-bend conformati on, two such conformations are consecutively formed by the tetrapeptid e. The pentapeptide adopts a regular 3(10)-helix promoted by three con secutive beta-bends. This study confirms the strong propensity of shor t peptides containing C(alpha)-methylated alpha-aminoacids to fold int o beta-bends and 3(10)-helical structures. Since Aib is achiral, the h andedness of the observed bends and helices is dictated by the presenc e of the (alphaMe)Phe residue. In general. we have found that the rela tionship between (alphaMe)Phe chirality and helix handedness is opposi te to that exhibited by protein aminoacids. A comparison with the pref erred conformation of other extensively investigated C(alpha)-methylat ed aminoacids is made.