Conformation of glycomimetics in the free and protein-bound state: structural and binding features of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man.
The conformational properties of the C-glycosyl analogue of the core trisaccharide alpha-D-Man-(1 --> 3)-[alpha-D-Man-(1 --> 6)]-D-Man in solution have been carefully analyzed by a combination of NMR spectroscopy and time-averaged restrained molecular dynamics. It has been found that both the alpha-1,3- and the alpha-1,6-glycosidic linkages show a major conformational averaging. Unusual Phi ca. 60 degrees orientations for both Phi torsion angles are found. Moreover, a major conformational distinction between the natural compound and the glycomimetic affects to the behavior of the omega(16) torsion angle around the alpha-1 --> 6-linkage. Despite this increased flexibility, the C-glycosyl analogue is recognized by three mannose binding lectins, as shown by NMR (line broadening, TR-NOE, and STD) and surface plasmon resonance (SPR) methods. Moreover, a process of conformational selection takes place, so that these lectins probably bind the glycomimetic similarly to the way they recognize the natural analogue. Depending upon the architecture and extension of the binding site of the lectin, loss or gain of binding affinity with respect to the natural analogue is found.
Mikkelsen
Lise Munch
LM
Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000 Aarhus C, Denmark.
Hernáiz
María José
MJ
Martín-Pastor
M
M
Skrydstrup
Troels
T
Jiménez-Barbero
Jesús
J
D040761:Biomimetic Materials / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D008358:Mannose / Q000031:analogs & derivatives* / Q000737:chemistry; D008362:Mannosides / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D014312:Trisaccharides / Q000737:chemistry*
C472424:Man-(1-3)-(Man-(1-6))-Man; D008362:Mannosides; D014312:Trisaccharides; D008358:Mannose