Efforts toward deriving the CD spectrum of a 310 helix in aqueous medium

FEBS Letters

Andersen, Niels H.²  Liu, Zhihong²  Prickett, Kathryn S.¹ 

[1] Amylin Pharmaceuticals Inc., 9373 Towne Centre Drive, San Diego, CA 92121, USA;Department of Chemistry, University of Washington, Box 351700, Seattle, WA 98195, USA

关键词: Circular dichroism;    Helix length effect;    310 Helix;    Aib-rich peptide sequence;   

DOI  :  10.1016/S0014-5793(96)01279-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

There have been two recent reports suggesting that 3₁₀ helices can be distinguished from α helices by circular dichroism. The differentiating feature is stated to be a [θ]₂₂₂:[θ]₂₀₈ ratio (R2) distinctly smaller than unity. This has been reported for a C_α,α′-disubstituted homooctamer [Toniolo et al. (1996), J. Am. Chem. Soc. 118, 2744–27451 and for alanine-rich systems of 16–21 residue length with modest fractional helicity [Millhauser (1995) Biochemistry 34, 3873–38771. We report here the changes in the CD spectrum produced by inserting aminoisobutyric acid (Aib) residues into the helical domain of human pancreatic amylin. In order to examine this effect at comparable net fractional helicities, CD spectra were measured for each species during the course of a helicity titration by trifluoroethanol addition. The addition of five Aib residues gave results of particular interest. At low net fractional helicity, this Aib-rich system displays a diminished (circa 208 nm) rotational strength versus the less Aib-rich species. However, NMR data and comparisons of CD difference spectra suggest that fluoroalcohol-induced extension of the short Aib-rich helix is in the form of an α helix. Given the diminished intensity of the minimum at 208 nm at low net helicity when 3₁₀ conformations should contribute, we urge extreme caution in using a [θ]₂₂₂:[θ]₂₀₈ ratio smaller than unity as a diagnostic for 3₁₀ helices.

【 授权许可】

Unknown