Consistent Helicities from CD and Template t/c Data for N-Templated Polyalanines:  Progress toward Resolution of the Alanine Helicity Problem

• Published in: Journal of the American Chemical Society 2002-02, Vol.124 (6), p.934-944
• Main Authors: Kennedy, Robert J., Tsang, Kwok-Yin, Kemp, Daniel S.
• Format: Article
• Language: English
• Subjects: Alanine - chemistry; Algorithms; Applied sciences; Biological and medical sciences; Circular Dichroism; Conformational dynamics in molecular biology; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Models, Chemical; Molecular biophysics; Oligopeptides - chemistry; Organic polymers; Peptides - chemistry; Physicochemistry of polymers; Properties and characterization; Protein Conformation; Solution and gel properties; Solutions; Templates, Genetic; Water - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja016285c

The helicity reporting parameters t/c and [θ]222 have been measured at 2, 25, and 60 °C in water for the solubilized polyalanine series Ac-Hel-A n - t LInp2K4W-NH2 of length 4 ≤ n ≤ 14 that bears the helix-initiating and monitoring N-cap Ac-Hel and the spaced solubilizer t LInp2K4W-NH2 as a C-cap. Correlation of t/c with length shows that the helical propensity for n ≤ 6 is ca. 1.0, consistent with our early reports, but that a dramatic increase in temperature dependence and helical propensity occurs for n ≥ 8. A model based on hydrogen-bonding cooperativity is proposed to explain this finding, and both t/c and [θ]222 are modeled successfully by length-dependent alanine propensities at 2 °C of 1.03 for n = 6, 1.15, for 7 ≤ n ≤ 9 and 1.26 for n ≥ 10. The implications of these results for the energetics of helix formation by alanine-rich peptide sequences are discussed.