Solution conformations of GM3 ganglioside containing different sialic acid residues as revealed by NOE-based distance mapping, molecular mechanics, and molecular dynamics calculations

Abstract

The conformation of the GM3 ganglioside, Neu5Aca2-3Gal/3l-4Glc/3lC1-e r, and its analogs containing the Neu5Gc or Neu4AcSGc residues (Gc = glycolyl, CH2OHCO) was investigated in Me2SO-ds solution with the aid of a distance-mapping procedure based on rotating-frame NOE contacts, with hydroxyl protons being used as long-range sensors defining the distance constraints. A pronounced flexibility found for both the Neu-Gal and Gal-Glc linkages was confirmed by 1 000-ps molecular dynamics simulations. Similar results, although based on a smaller number of NOE constraints, were obtained for GM3 gangliosides anchored in mixed D20/dodecylphosphocholine-d38 micelles and for the NeuSAc-, NeuSGc-, and Neu5,9Ac~-sialyllactoses dissolved in D20. No noteworthy differences in conformational behavior of the glycan chains of the three gangliosides or sialyllactoses were observed in either of the media