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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.

Authors
  • Mikkelsen, Lise Munch
  • Hernáiz, María José
  • Martín-Pastor, M
  • Skrydstrup, Troels
  • Jiménez-Barbero, Jesús
Type
Published Article
Journal
Journal of the American Chemical Society
Publication Date
Dec 18, 2002
Volume
124
Issue
50
Pages
14940–14951
Identifiers
PMID: 12475336
Source
Medline
License
Unknown

Abstract

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.

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