Carbohydrates, modification

In some instances, reducing sugars are present that can be reductively aminated without prior periodate treatment. A reducing end of a monosaccharide, a disaccharide, or a polysaccharide chain may be coupled to a diamine by reductive amination to yield an aminoalkyl derivative bound by a secondary amine linkage (Figure 1.96). Also see Section 4.6, this chapter, for an extensive discussion on carbohydrate modification techniques. 

PHYSICAL ORGANIC CHEMISTRY NO-MENCATURE CARBOCATION CARBENIUM ION CARBONIUM ION BRIDGED CARBOCATION CARBOHYDRATE MODIFICATION REACTIONS... 

Carbohydrate Modification Is Crucial to Targeting Lysosomal Enzymes... 

Manoharan, M. 1999. 2 -Carbohydrate modifications in antisense oligonucleotide therapy importance of conformation, configuration and conjugation. Biochim. Biophys. Acta 1489 117-130. 

Other methods of stabilization include chemical or carbohydrate modification of enzymes. Modifications of reactive groups on proteins without insolubilization has been used to enhance stability in solution. Grafting of polysaccharides or synthetic polymers, alkalation, acetylation and amino acid modification have all been reported (5)... 

Mattes MJ. Biodistribution of antibodies after intraperitoneal or intravenous injection and effect of carbohydrate modifications. J Natl Cancer Inst 1987 79(4) 855—63. 

Glycosylation. Carbohydrate modifications of proteins (glycosylation) are key factors in modulating protein structures and functions within cells. Glycosylation affects probably more than half of all proteins in a eukaryotic cell [40]. In the extracellular environment, the oligosaccharide moieties of... 

Attempts at changing the fate of compounds in vivo by means of carbohydrate modification are not confined to EPO. For example, it has been reported that new functional characteristics (e. g., prolonged half-life in blood, improved solubility in water, etc.) can be achieved by attaching carbohydrates to particular positions of compounds, e. g., thrombopoietin with only 0-linked carbohydrate [32] and insulin without any carbohydrates [33,34]. Thus, carbohydrate modification is being acknowledged as a useful technique for modifying the functions of proteins. 

There are many unresolved questions over the relationship of carbohydrate structure to antibody activity, kinetics and specificity. However, it is evident that the carbohydrate structure greatly affects the antibody functions. Attempts at improving the functions of antibodies by means of carbohydrate modification are now viewed as valuable from the standpoint of their potential for commercialization [43,44]. 

Controversial results have been reported on the relation between the genetic group and the infectivity of an isolate.5-7 Most T. cruzi proteins are heavily glycosylated, and the carbohydrate modification is strongly dependent on the life cycle and original lineage of the parasite, as described in the following sections of this chapter. 

Numerous procedures for the conjugation of antibodies to lipcsomes have been developed (13-16). These fall into four general categories defined by the particular functionality of the antibody being modified, namely amine modification, carbohydrate modification, disulfide modification, and noncovalent conjugation, each of which will be discussed below. These procedures are very similar to those used to prepare affinity columns (17), except for modifications made to accommodate the fact that the substrate is in the solution phase rather than the solid phase. 

Although many proteins contain the modB carbohydrate, most of the attention has been on the analysis of two of them. One is a cell surface glycoprotein, called PsA (a.k.a. SP29), which has been cloned and sequenced. The carbohydrate modifications are located on a repeated motif, PTVT as shown by Edman degradation [68]. This sequence is typical of many of those in mammalian cell proteins which also contain O-Iinked oligosaccharides [69]. Several allelic variants of this protein from related strains of Dictyostelium discoideum contain 3-5 of these glycosylated repeats [70]. This protein... 

More substantial carbohydrate modifications have also been studied (Fig. 5.8). The 4 -oxygen has been replaced with sulfur. Although a single substitution of a 4 -thio-mod-ified nucleoside resulted in destabilization of a duplex, incorporation of two 4 -thio-modified nucleosides increased the affinity of the duplex (3 52). Also, hexose-containingoligonucle-... 

Y. S. Sanghvi and P. D. Cook, Carbohydrate Modifications in Antisense Research, ACS Symposium Series580, American Chemical Society, Washington, DC, 1994. 

---