Ml. Smythe et al., ALPHA-HELICAL VERSUS 3(10)-HELICAL CONFORMATION OF ALANINE-BASED PEPTIDES IN AQUEOUS-SOLUTION - AN ELECTRON-SPIN-RESONANCE INVESTIGATION, Journal of the American Chemical Society, 117(42), 1995, pp. 10555-10562
Due to the difficulties in experimentally differentiating between the
alpha- and 3(10)-helical conformations in solution, isolated helical p
eptides have been assumed to be in the alpha-helical conformation. How
ever, recent electron spin resonance (ESR) studies have suggested that
such peptides, in particular short alanine-based peptides, are 3(10)-
helical (Miick, S. M.; et al. Nature 1992, 359, 653-5). This result pr
ompted us to further investigate the helical conformations of alanine-
based peptides in solution using electron spin resonance spectroscopy.
Unlike previous investigations with a flexible link connecting the sp
in-label to the peptide backbone, we used a conformationally constrain
ed spin-label no-4-carboxy-2,2,6,6-tetramethylpiperidine-1-oxyl, Toac)
that is rigidly attached to the peptide backbone. From a combination
of molecular modeling and ESR spectroscopy investigations, it was conc
luded that these alanine-based peptides exist primarily in the alpha-h
elical conformation, and not the 3(10)-form as previously suggested fo
r an analogous set of peptides in aqueous environments. This discrepan
cy is thought to be due to the differences in flexibility of the spin-
labels employed. The conformationally constrained spin-label Toac used
in this study should accurately reflect the backbone conformation. Fr
ee energy surfaces, or potentials of mean force, for the conformationa
l transition of the spin-label used in previous studies (Miick S. M.;
et al. Nature 1992, 359, 653-5) suggest that this spin-label is too fl
exible to accurately distinguish between the alpha- and 3(10)-helical
conformations.