34 化学シフト予測法を用いるオリゴ糖と超分子の立体配座解析(口頭発表の部)

抄録

Identification of significant populating conformers in extremely flexible molecules is a matter of long standing interest. We have developed a useful and very reliable method for conformational analysis of a flexible compound using the information obtained from the chemical shifts. It is based on the chemical shift simulation method which utilized the calculation of the change in proton chemical shifts produced by nearby aromatic ring. In this paper we report a successful application of our method to the conformational analysis of an oligosaccharide in aqueous solution using molecular dynamics calculations. The tetrasaccharide sialyl Lewis^X derivatives have known to be a ligand for endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin). We selected the sialyl Lewis^X derivatives (1-3) for the conformational analysis. Our method consists of four stages: 1) the generation of the probable structures, 2) estimation of the induced proton shifts in these structures caused by the aromatic ring, 3) the selection of the most likely conformers by comparison of the observed and calculated induced shift, and 4) molecular dynamics simulation starting from these candidate structures to obtain a conformer which satisfying the observed induced shifts. According to our strategy, we obtained a converged structure by the molecular dynamics simulation with Amber^* force field. It gave a satisfying agreement of the induced shifts of 25 C-H protons of the five saccharide units with those of the observed. (R^2=0.90)