Molecular carbohydrate recognition

This paper is not a review covering the entire field of carbohydrate-recognition in any organized system. Many excellent papers have already been devoted to supramolecular systems such as cyclodextrins, podands, coronands or cryptants able to entrap carbohydrate molecules [1]. This article only deals with the molecular recognition of mono and oligosaccharides in organized self-assemblies of amphiphilic carbohydrates (possibly blended with other lipids) in aqueous medium i.e. in assemblies mimicking the cell membrane. 

Several evidences, reported in the literature and briefly reviewed in the present article, demonstrate that the carbohydrate recognition at the surface of organized systems is somewhat different from that observed in isotropic media. These differences lie in (1) the conformation of carbohydrate which is affected by hydrophobization and by the nature of the surrounding lipids, (2) cluster effects from which can result in high energies of binding and which are affected by the fluidity of the lipid system, (3) entropy changes at the surface of a supra-molecular structure. 

Lowe JB (1994) Carbohydrate recognition in cell-cell interaction. In Fukuda M, Hindsgaul O (eds) Frontiers in Molecular Biology, Molecular Glycobiology. IRL Press, Oxford, p 163... 

Pichierri, F, Matsuo, Y, Effect of protonation of the A-acetyl neuraminic acid residue of sialyl Lewis a molecular orbital study with insights into its binding properties toward the carbohydrate recognition domain of E-selectin, Bioorg. Med. Chem. Lett., 10, 2751-2757, 2002. 

Fig. 2. Summary of structural features of C-type animal lectins. The (nearly) invariant residues found in the coimnon carbohydrate-recognition domain of the C-type lectins are shown, flanked by schematic diagrams of the special effector domains (if any) found in individual members of the family. GAG, glycosaminoglycan EGF, epidermal growth factor. Reproduced from K. Drickamer, Two Distinct Classes of Car bohydrate-recognition Domains in Animal Lectins, J. Biol. Chem., 263 (1988) 9557-9560 (Ref. 35) 1988. The American SocietyforBiochemistry Molecular Biology with permission by Professor Kurt Drickamer and The American Society for Biochemistry Molecular Biology.

The small size of hevein (43 residues), and the ease of its availability by biochemical purification or methods of peptide synthesis make this domain an excellent model system for the study of carbohydrate recognition by proteins. Herein, and taking the hevein domain as a model, we focus on the study of those molecular-recognition features relevant for the interactions between carbohydrates and proteins. We detail all of the techniques that are instrumental for tackling this problem, and how these can strategically be combined in an efficient manner. Particular emphasis is placed on the acquisition and analysis of data at atomic resolution (by NMR and/or X-ray ), and how these structural data relate with thermodynamic and kinetic information in reaching an understanding of the forces and interactions that play decisive roles in the interactions between carbohydrates and proteins. 

Glycoproteins are essential to many basic cellular and disease processes including molecular/cellular recognition, intracellular sorting, cell growth, fertilization, immune defense, inflanunation, tumor metastasis, viral replication and bacterial/parasite infection. For example, carbohydrates of glycoproteins at the manunalian cell surface have two major functions. Inside the cell, they help proteins fold and assemble correctly in the... 

It should be noted that carbohydrate recognition through formation of boronates has been remarkably successful. However, it involves covalent bonds and cannot be seen as biomimetic. For reviews, see James, T. D., Sandanayake, K. R. A. S. and Shinkai, S. (1996) Saccharide sensing with molecular receptors based on boronic acid, Angew. Chem., Int. Ed. Engl. 35, 1911-1922 Smith, B. D. (1996) Liquid membrane transport using boronic acid carriers, Supramolecular Chemistry 7, 55-60. 

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