Enzymes in Organic Synthesis: Application to the Problems of Carbohydrate Recognition (Part 2)

Authors

  • Prof. Dr. Chi-Huey Wong,

    Corresponding author
    1. Department of Chemistry, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037 (USA). Telefax: Int. code + (619)554-6731
    • Department of Chemistry, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037 (USA). Telefax: Int. code + (619)554-6731
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  • Dr. Randall L. Halcomb,

    1. Department of Chemistry, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037 (USA). Telefax: Int. code + (619)554-6731
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  • Prof. Dr. Yoshitaka Ichikawa,

    1. Department of Pharmacology and Molecular Sciences, The Johns Hopkins University, Baltimore (USA)
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  • Dr. Tetsuya Kajimoto

    1. Frontier Research Program on Glycotechnology, The Institute of Physical and Chemical Research (RIKEN), Wako City (Japan)
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  • Part 1: Angew. Chem.1995, 107, 453; Angew. Chem. Int. Ed. Engl.1995, 34, 412. The numbering of the sections, references, schemes, and Tables follows on from Part 1.

Abstract

Recognition of carbohydrates by proteins and nucleic acids is highly specific, but the dissociation constants are relatively high (generally in the mM to high μM range) because of the lack of hydrophobic groups in the carbohydrates. The high specificity of this weak binding often comes from many hydrogen bonds and the coordination of metal ions as bridge between sugars and receptors. Though weak hydrophobic interactions between sugars and proteins have also been identified, the unique shape of a complex carbohydrate under the influence of anomeric and exo anomeric effects (the glycosidic torsion angles are therefore often not flexible but are typically somewhat restricted) and the topographic orientation of the hydroxyl and charged groups contribute most significantly to the recognition process. Studies on the structure–function relationship of a complex carbohydrate therefore require deliberate manipulation of its shape and functional groups, and synthesis of oligosaccharide analogs from modified monosaccharides is often useful to address the problem. The availability of various monosaccharides and their analogs for the synthesis of complex carbohydrates together with the information resulting from structural studies (such a NMR or X-ray studies on sugar–protein complexes) will certainly provide a basic understanding of complex carbohydrate recognition. An ultimate goal is to develop simple and easy-to-make non-carbohydrate molecules that resemble the active structure involved in carbohydrate–receptor interaction or the transition-state of an enzyme-catalyzed transformation (for example, glycosidase or glycosyltransferase reactions) and have the approprite bioavailability to be used to control the carbohydrate function in a specific manner. In part one of this review we described various enzymatic approaches to the synthesis of monosaccharides, analogs, and related structures. We describe in this part enzymatic and chemoenzymatic approaches to the synthesis of oligosaccarides and analogs, including those involved in E-selectin recognition, and strategies to inhibit glycosidases and glycosyltransferases.

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