Structural Versatility of Peptides From C-alpha,alpha-disubstituted Glycines - Synthesis, Characterization, and Solution Conformational-analysis of Homopeptides From C-alpha-methyl-c-alpha-benzylglycine, [(alpha-me)phe]n(1)

A complete series of N- and C-blocked, monodispersed homooligopeptides from the sterically hindered (alpha-Me)Phe residue to the pentamer level was synthesized step-by-step by solution methods and fully characterized. The preferred conformation in chloroform solution was determined by FT-IR and H-1 NMR as a function of concentration and addition of a perturbing agent. In particular, the results obtained strongly support the view that a series of three consecutive beta-turns (3(10)-helix) is preferentially adopted by the pentamer, a clear indication that the (alpha-Me)Phe residue is an efficient beta-turn and helix former, much stronger than its unmethylated parent compound (Phe). A comparison is also made with the conclusions extracted from a published work on homopeptides from Aib, the prototype of C(alpha,alpha)-disubstituted glycines.