STRUCTURAL VERSATILITY OF PEPTIDES FROM C-ALPHA,ALPHA-DISUBSTITUTED GLYCINES - SYNTHESIS, CHARACTERIZATION, AND SOLUTION AND CRYSTAL-STATE CONFORMATIONAL-ANALYSIS OF HOMOPEPTIDES FROM C-ALPHA-METHYL-C-ALPHA-ISOPROPYLGLYCINE, [(ALPHA-ME)VAL]

Terminally blocked homodi- and homotripeptides from (alphaMe)Val, a C( alpha,alpha)-disubstituted glycine, were prepared by solution methods and fully characterized. The preferred conformation in chloroform solu tion was assessed by FT-IR and H-1 NMR as a function of concentration and addition of perturbing agents. The molecular and crystal structure s of the dipeptide and tripeptide amides, Z-[D-(alphaMe)Val]n-NHiPr (n = 2, 3) were also determined by X-ray diffraction. While the dipeptid e amide adopts a type-III' beta-turn conformation stabilized by a 1 <- - 4 C=O...H-N intramolecular H bond, the tripeptide amide is folded in an incipient left-handed 3(10)-helix. These results confirm that (i) the (alphaMe)Val residue is an effective beta-turn and helix promoter and (ii) the relationship between (alphaMe)Val chirality and helix scr ew sense is the same as that exhibited by protein amino acids. A compa rison is made with the conclusions obtained from published work on hom opeptides from other C(alpha)-methylated alpha-amino acids.