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-GlcNAc-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-PhiPsi conformer, and thus a conformational selection process is correlated with the molecular recognition event.
García-Aparicio
Víctor
V
Ecole Normale Supérieure, Département de Chimie, UMR CNRS 8642, 24, rue Lhomond, 75231 Paris Cedex 05, France.
Sollogoub
Matthieu
M
Blériot
Yves
Y
Colliou
Virginie
V
André
Sabine
S
Asensio
Juan L
JL
Cañada
F Javier
FJ
Gabius
Hans-Joachim
HJ
Sinaÿ
Pierre
P
Jiménez-Barbero
Jesús
J
D000117:Acetylglucosamine / Q000737:chemistry; D000606:Amino Sugars / Q000737:chemistry*; D002236:Carbohydrate Conformation; D002448:Cell Adhesion; D002455:Cell Division; D004187:Disaccharides / Q000737:chemistry; D037483:Galectin 1 / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D037121:Plant Lectins / Q000737:chemistry / Q000633:toxicity*
D000606:Amino Sugars; D004187:Disaccharides; D037483:Galectin 1; D006027:Glycosides; D037121:Plant Lectins; C032233:lactosamine; D000117:Acetylglucosamine