Water-Soluble Polypeptides with Elongated, Charged Side Chains Adopt Ultra-Stable Helical Conformations.

Water-soluble polypeptides adopting α-helical conformations with unprecedented high helicities were obtained by elongating the charge-containing side chains of the constituent amino acids to allow the terminal charges to be situated distally from the peptide backbone. Poly(γ-(4-aminoethylthiopropoxyl)-benzyl-(L)-glutamate) (PAOBLG-AET) with a charge-peptide backbone distance of 17 σ-bonds exhibited a remarkably high helical content (81%) at a degree of polymerization as low as 10. The helical conformations of these short polypeptides were very stable against various harsh, protein-denaturing conditions, such as extreme pH, high temperature, and high salt or urea concentrations.