Improved method for the stereospecific1H-NMR assignments in collagen-like triple-helices

Abstract

An improved model-based method for the stereospecific assignment of prochiral centers in collagen-like triple-helical molecules is introduced. Using the concepts of reporter atoms and of ensemble NOEs, the proposed methodology extracts the stereochemical information contained in the chiral elements of triple-helices and transfers it to prochiral centers with nondegenerate proton resonances. The improved approach has been successfully validated using -(Gly-Pro-Hyp)n- triple-helices for which the stereospecific assignment was previously obtained with established techniques. We have applied our stereochemical characterization to novel peptoid containing triple-helices for which existing methods of stereospecific assignment can not be used for all the prochiral centers. In our approach, several different NOE measurements are employed to make a given stereospecific assignment. The multiple NOE comparisons allow internal cross checks, which reduce the chance of erroneous assignments caused by experimental artifacts including spin diffusion and bias from anisotropic rotational motions. In addition, the multiple NOE comparisons are useful in overcoming problems associated with resonance overlap often encountered in the 1H-NMR spectra of collagen-like molecules. Our stereochemical analysis is anticipated to improve the precision and accuracy of the characterization of collagen-like triple-helices through a better correlation of structures with their 1H-NMR spectra. Chirality 10:28–34, 1998. © 1998 Wiley-Liss, Inc.