C-alpha-Methyl, C-alpha-n-Propylglycine Homo-oligomers

A series of Nα-protected, monodispersed homo-oligopeptide esters to the octamer level from l-Cα-methyl, Cα-n-propylglycine [or Cα-methylnorvaline, (αMe)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 1H 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 β bends are preferentially adopted by the conformationally restricted l-(αMe)Nva homo-oligomers. In particular, 310 helices are formed by the longest homo-oligomers. It is our contention that the [(αMe)Nva]n peptides represent the best available choice among Cα-tetrasubstituted α-amino acid-based homo-oligomers for the construction of relatively easy to make, rigid foldamers with a well-defined screw-sense bias.