C-alpha-methyl, C-alpha-n-propylglycine homo-oligomers

A series of N-alpha-protected, monodispersed homo-oligopeptide esters to the octamer level from L-C-alpha-methyl, C-alpha-n-propylglycine [or C-alpha-methylnorvaline, (alphaMe)Nva] has been synthesized by solution methods and fully characterized. The preferred conformation of these homo-oligomers in solution has been assessed by FT-IR absorption and H-1 NMR techniques. Moreover, the molecular structures of the homotrimer and homotetramer have been determined in the crystal state by X-ray diffraction. The obtained results strongly support the view that right-handed, single or multiple, and consecutive beta bends are preferentially adopted by the conformationally restricted L-(alphaMe)Nva homo-oligomers. In particular, 3(10) helices are formed by the longest homo-oligomers. It is our contention that the [(alphaMe)Nva](n) peptides represent the best available choice among C-alpha-tetrasubstituted alpha-amino acid-based homo-oligomers for the construction of relatively easy to make, rigid foldamers with a well-defined screw-sense bias.