First homo-peptides undergoing a reversible 3(10)-helix/alpha-helix transition: Critical main-chain length

The difference in length between the more elongated peptide 3(10)-helix and the more compact alpha-helix is about 0.4 angstrom/residue. This property makes the 3(10)-/alpha-helix reversible conversion very promising as a molecular switching tool between the N- and C-terminal functions of a peptide backbone. In this work, using homo-pepticles Of various main-chain length, all based on the strongly helicogenic, C-alpha-tetrasubstituted alpha-amino acid C-alpha-methyl-L-valine, we show that a well defined, solvent controlled, reversible 3(10)-/alpha-helix transition takes place even in a homo-oligomer as short as a terminally blocked hexapeptide. Homo-peptide sequences blocked as a urethane or an acetamide at the N-tcrminus and as a methyl ester or an N-alkyl amide at the C-terminus are all appropriate. The nature of the occurring helical species in the various solvents tested was assessed by electronic or vibrational circular dichroism.