Carbohydrate mimetics

Carbohydrate mimetics including heterocyclic fragments and a new strategy for tackling the problem of biological recognition with participation of carbohydrates 99AG(E)2300. 

P. Sears, C.-H. Wong, Carbohydrate Mimetics A New Strategy for Tackling the Problem of Carbohydrate-Mediated Biological Recognition , Angew. Chan. Int. Ed 1999, 38, 2300-2324. 

NMR has also been of crucial importance to derive key information on the emerging development of new carbohydrate mimetic structures. 

It is clear that protein-carbohydrate interactions are essential in numerous biological processes and that the development of carbohydrate mimetics that interfere with these processes would provide a powerful methodology for both modulation and amelioration of specific biological activity. Since the early 1990s, novel... 

These initial reports showed that functional carbohydrate-mimetic peptides could be found. These peptides acted as ligands for several biologically important proteins, and had potential in the development of therapeutics. Subsequently, peptides that act as molecular mimics of carbohydrates in binding to a wide variety of different receptors have been identified [ 14-44] these are summarized in Table 1 and reviewed in [ 13]. Some of these peptides were able not only to bind to a particular receptor, but also to act as immunologically functional mimics and to induce an anti-carbohydrate immune re-... 

Table 2 Mimotopes, or carbohydrate-mimetic peptides capable of inducing anti-...

The interactions of carbohydrate-mimetic peptides with anti-GAS Abs have also been investigated. 

Clearly, further studies will be necessary to sort out the multiple factors involved in the in vivo immune response to C. neoformans carbohydrate-mimetic peptides. Several conclusions may be drawn from the results to date. Peptides that mimic the cryptococcal capsular polysaccharide show specificity, in that each peptide binds with differing affinity to closely related mAbs [140,149]. The pattern of binding to protective and nonprotective mAbs differs between the mimetic peptides and the polysaccharide [140]. Protective efficacy is related to the location of carbohydrate epitopes recognized by these mAbs, within the polysaccharide capsule, but hkely also depends on interactions between mAbs and cellular responses [149]. Peptides have been shown to be functional, immunogenic mimics, but their protective efficacy depends on multiple factors, including the type of Abs elicited and interactions with the cellular immune system. Protective efficacy does not correlate with binding affinity to representative mAbs, but rather depends on the nature of these interactions. 

One of the earliest reported carbohydrate-mimetic peptides was the dodecapeptide DVFYPYPYASGS [10]. The peptide acts as a ligand for con-canavalin A, a lectin which binds oligosaccharides bearing terminal a-linked... 

New Applications and Challenges for the Therapeutic Use of Carbohydrate-Mimetic Peptides... 

The binding affinity of carbohydrate-mimetic peptides can be quite high, often higher than the natural carbohydrate ligand. Carbohydrate-mimetic peptides do not share any general chemical features, and all amino acid residues are represented there is no evidence for an unusual importance of aromatic residues in mimicry. In several cases, o-amino acids have been incorporated, and unusual amino acids (derived from nonribosomal peptide synthesis) have been found in naturally occurring carbohydrate-mimetic peptides. 

Starting from bioactive proteins, peptides with similar activity or binding properties could frequently be identified the development of peptide mimetics from those peptides is a classical exercise in medicinal chemistry. The analogous approach for carbohydrates, the development of carbohydrate mimetics from bioactive polysaccharides, is in its infancy. 

H. J. M. Gijsen, L. Qiao, W. Fitz, and C.-H. Wong. Recent advances in the chemoenzymatic synthesis of carbohydrates and carbohydrate mimetics, Chem. Rev. 96 443 (1996). 

Vyacheslav V. Samoshin was born in Norilsk, Russian Federation. He graduated with an Honorable Diploma (M.S.) from Moscow State University in 1974. At the same university, he defended his Ph.D. dissertation under the supervision of academician Nikolay S. Zefirov in 1982, and his Doctor of Chemical Sciences dissertation in 1991. He worked as a researcher in the Department of Chemistry, Moscow State University, and since 1992 as professor (head of the Division of Organic Chemistry in Moscow State Academy of Fine Chemical Technology). In 1999, he took his present position as professor of chemistry at the University of the Pacific, Stockton, California. His scientific interests include molecular switches, conformational analysis, synthesis and studies of bioactive compounds, including carbohydrate mimetics, asymmetric synthesis, and synthesis and studies of crown ethers and relative compounds. 

Johnson, M. A., Rotondo, A. and Pinto, B. M. (2002) NMR studies of the antibody-bound conformation of a carbohydrate-mimetic peptide. Biochemistry 41, 2149-2157. 

DESIGN AND SYNTHESIS OF CARBOHYDRATES AND CARBOHYDRATE MIMETICS AS ANTI-INFLUENZA AGENTS... 

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