Neoglycoproteins

Neoglycoproteins (Stowell and Lee, 1980) refer to synthetic glycoproteins by chemically attaching mono- or oligosaccharides to proteins directly or via spacers. Table 6.9 lists examples of neoglycoproteins and their synthetic methods. 

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Synthetically produced or modified carbohydrate-protein conjugates are sometimes referred to as neoglycoproteins. The nomenclature for the carbohydrate-containing substituents in such structures is analogous to sequential oligosaccharide nomenclature (2-Carb-37.2)... 

Source Courtesy of Professor D. K. F. Meijer, University Center of Pharmacy, University of Groningen, Groningen, The Netherlands. Other examples of drug targeting with glycoproteins and neoglycoproteins can be found in Ref. 235. 

P. Chakraborty, A. N. Bhaduri, and P. K. Das, Neoglycoproteins as carriers for receptor-mediated drug targeting in the treatment of experimental visceral leishmaniasis, J. Protozool., 37 (1990) 358-364. 

Some reports even indicate that the conjugation of proteins or peptides with carbohydrates can increase dramatically their activity compared to that of the native state (Susaki et al., 1998). Carbohydrates also can provide a protective effect on modified peptides toward proteolytic digestion (Rudd et al., 1994) or mask recognition of a peptide by the immune system (Harding et al., 1993). The creation of neoglycoproteins thus can affect the activity of peptides and proteins, which are not normally glycosylated in vivo. 

The latter approach has been followed in our laboratory. For instance, in studies related to the synthesis of potent multivalent sialoside inhibitors of influenza virus hemagglutinin [34], it became of interest to evaluate the immunogenicity of neoglycoproteins containing sialosides as sole immunodominant hapten. To this end, acetochloroneuraminic acid (1) was transformed into allyl glycoside 2 (Scheme 1) which upon reductive ozonolysis afforded aldehyde 3 in excellent overall yields [35], Reductive amination of 3 to bovine serum albumin (BSA) and tetanus toxoid provided immunogenic vaccines from which specific rabbit IgG anti-sialic acid antibodies were obtained [36]. In order... 

In the preparation of affinity adsorbents, it is necessary to attach the ligand residues to insoluble supports by chemical bonds or physical interactions. Adsorbents having carbohydrate ligands have been prepared for the most part by chemical reaction of carbohydrate derivatives with the support material. Methods for the preparation of some types of carbohydrate derivatives are described in Section IV. Methods for the preparation of other derivatives of carbohydrates that may be suitable for synthesizing affinity adsorbents have been described in an article on neoglycoproteins.31... 

Because O-glycosylation can also be accomplished with active esters (e.g., penta-fluorophenyl esters) [11] of Fmoc serine and threonine, the Fmoc technique provides a general method for the synthesis of glycopeptides. Thomsen-Friedenreich antigen glycopeptides and neoglycoproteins have been obtained by this method in preparative amounts [12], In combination with acid-labile polymeric benzyl ester anchors, this Fmoc technique was applied to solid-phase syntheses of glycopeptides [11,13,14]. 

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