Efforts toward deriving the CD spectrum of a 3(10) helix in aqueous medium.
There have been two recent reports suggesting that 3(10) helices can be distinguished from alpha helices by circular dichroism. The differentiating feature is stated to be a [theta]222:[theta]208 ratio (R2) distinctly smaller than unity. This has been reported for a C(alpha)alpha'-disubstituted homooctamer [Toniolo et al. (1996), J. Am. Chem. Soc. 118, 2744-2745] and for alanine-rich systems of 16-21 residue length with modest fractional helicity [Millhauser (1995) Biochemistry 34, 3873-3877]. 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 pi-->pi* (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 alpha helix. Given the diminished intensity of the minimum at 208 nm at low net helicity when 3(10) conformations should contribute, we urge extreme caution in using a [theta]222:[theta]208 ratio smaller than unity as a diagnostic for 3(10) helices.
Andersen
N H
NH
Department of Chemistry, University of Washington, Seattle 98195, USA. andersen@chem.washington.edu
Liu
Z
Z
Prickett
K S
KS
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D010455:Peptides; D014867:Water