ESI fragmentation studies of six unusual nucleotide sugars / 药学学报

Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with collision-induced dissociation (CID) was used to study the fragmentation characteristics of six unusual nucleotide diphosphate sugars. The results indicated the major fragment of the six unusual nucleoside sugars observed in the ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H] together with fragment ions resulting from the loss of water and phosphate moiety, respectively. Furthermore, 4-position substituted change of unusual sugar rings affected the stability of two important characteristic fragment ions of [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).

Nucleotide-sugar transporters: structure, function and roles in vivo

The glycosylation of glycoconjugates and the biosynthesis of polysaccharides depend on nucleotide-sugars which are the substrates for glycosyltransferases. A large proportion of these enzymes are located within the lumen of the Golgi apparatus as well as the endoplasmic reticulum, while many of the nucleotide-sugars are synthesized in the cytosol. Thus, nucleotide-sugars are translocated from the cytosol to the lumen of the Golgi apparatus and endoplasmic reticulum by multiple spanning domain proteins known as nucleotide-sugar transporters (NSTs). These proteins were first identified biochemically and some of them were cloned by complementation of mutants. Genome and expressed sequence tag sequencing allowed the identification of a number of sequences that may encode for NSTs in different organisms. The functional characterization of some of these genes has shown that some of them can be highly specific in their substrate specificity while others can utilize up to three different nucleotide-sugars containing the same nucleotide. Mutations in genes encoding for NSTs can lead to changes in development in Drosophila melanogaster or Caenorhabditis elegans, as well as alterations in the infectivity of Leishmania donovani. In humans, the mutation of a GDP-fucose transporter is responsible for an impaired immune response as well as retarded growth. These results suggest that, even though there appear to be a fair number of genes encoding for NSTs, they are not functionally redundant and seem to play specific roles in glycosylation.