4 - α-Helix Formation by Peptides in Water

Abstract

This chapter elucidates the use of peptide helices to analyze the factors that determine protein stability: helix propensities and specific interactions between side chains. Most of the advances in the field of helix formation by peptides are due to the increased availability of solid-phase peptide synthesis methods. The initial studies in the field were directed toward an understanding of helix formation in water by the 13-residue C-peptide from the N terminus of ribonuclease A. The C-peptide and other model systems derived from proteins offer excellent systems for examining the qualitative roles of side-chain interactions as well as the effects of specific amino acid substitutions on helix formation. The C-peptide system was very complex as a host peptide for studying all the specific elements of helix formation in peptides. The major advancement in the peptide helix field came with the design of short peptide sequences that showed a good α-helix formation in water. With the availability of several de novo designed peptide systems, the interest has been revived in measuring the intrinsic helix-forming tendencies or helix propensities of all of the amino acids, and also in analyzing the side-chain interactions that can help stabilize helices in an aqueous solution.