The conformation of the C-glycosyl analogue of N-acetyl-lactosamine in the free state and bound to a toxic plant agglutinin and human adhesion/growth-regulatory galectin-1

The conformational behavior of the C-glycoside analogue of N-acetyl-lactosamine, beta-C-Gal-(1 -> 4)-beta-GIcNAc-OMe, 1, has been studied using a combination of molecular mechanics calculations and NMR spectroscopy (J and NOE data). It is shown that the C-disaccharide populates three distinctive conformational families in solution, the major one being the anti-psi conformation. Of note, this conformation is only marginally populated for the O-disaccharide. Due to its conspicuous role in the regulation of adhesion, growth and tissue invasion of tumors and its avid binding to N-acetyl-lactosamine human, galectin-1 was tested as a receptor. This endogenous lectin recognizes a local minimum of 1, the syn-Phi Psi conformer, and thus a conformational selection process is correlated with the molecular recognition event. (c) 2007 Elsevier Ltd. All rights reserved.