The α-helix is one of a small number of fundamental structural motifs of the peptide backbone that are abundant in native proteins. The forces responsible for its stability have attracted a great deal of theoretical and experimental attention. Helix formation can naturally be considered in terms of two processes, initial nucleation of a helix from a sequence of disordered residues and propagation or growth of helical structure from such a nucleus. Data from a variety of short peptide and polypeptide models have revealed more details about the propagation of helix structure than about helix nucleation. To investigate helix nucleation, we have synthesized two series of high molecular weight polypeptides containing differing ratios of alanine and one of the basic side chains, ornithine or lysine; poly L-alanine is insoluble in water. The CD signals of these copolymers have been analyzed by a program that evaluates the helix content in terms of the experimental chain-length distribution and composition, with the helix nucleation constant (σ value) and the propagation constants (s values) for the amino acids involved. Fitting the CD data allows the determination of the propagation constants for Orn (s = 0.45) and Lys (s = 0.8) in addition to that of the helix nucleation constant once the s value for Ala is specified. The value of σ is sensitive to the dependence of the CD signal on helix length; using the Yang equation, [θ]222 = -41000(n - x)/n, with x = 2.5, the nucleation constant value is σ = 0.004 ± 0.002 at 4 °C in the presence of 1 M salt. This value is consistent with earlier estimates based on analysis of the helix-coil transition in poly(Lys), poly(Glu), and shorter Ala-rich peptides. However, if x is taken to be zero, the resulting σ value is 0.02, considerably larger than the above estimates.
ASJC Scopus subject areas
- Colloid and Surface Chemistry