Enzymatic in vitro synthesis of I-branches of mammalian polylactosamines: generation of scaffolds for multiple selectin-binding saccharide determinants.
Polylactosamines are covalent monosaccharide assemblies of the animal kingdom and some bacteria, and are characterized by backbones of interlinked N-acetyllactosamine units (Galbeta1-4GlcNAc, LacNAc). The mammalian LacNAc arrays are linear (blood group i-type) and branched (blood group I-type), and are linked to the core elements of glycolipids as well as O- and N-glycans of glycoproteins and keratan sulfate proteoglycans. Generation of I-branches to linear i-type polylactosamines is initiated by two kinds of beta6GlcNAc transferases. One type of the enzymes transfers to Glc-NAcbeta 1-3Galbeta 1-OR of growing i-chains at the peridistal (underlined) Gal; these enzymes are called dIGnT (d for 'distally acting'). The other enzymes transfer to internal Gal units of preformed i-chains; they are called cIGnT (c for 'centrally acting'). Purified natural and recombinant enzymes of both types have been described. The structures of I-type polylactosamines result from a collaboration of dIGnTs, cIGnTs, beta4GalTs and the i-chain-elongating iGnTs. At present, the interplay of these enzymes in vivo is poorly understood. By contrast, enzyme-assisted in vitro synthesis of branched polylactosamines representing distinct LacNAc arrays that are multiply capped by a variety of decorations is possible. Some of the synthetic polylactosamines reduce the lymphocyte-endothelium adhesion in a tissue-specific mode, raising the possibility of achieving local immunosuppression in the future. Useful applications of multiply decorated I-type polylactosamines may also be found in prevention of mammalian gamete adhesion and in inhibition of bacterial and viral adhesion to host tissues.
Renkonen
O
O
Institute of Biotechnology, University of Helsinki, Finland. ossi.renkonen@helsinki.fi
D000606:Amino Sugars / Q000096:biosynthesis*; D000818:Animals; D002240:Carbohydrate Sequence; D006801:Humans; D008322:Mammals; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D011134:Polysaccharides / Q000096:biosynthesis* / Q000378:metabolism*; D019087:Selectins / Q000378:metabolism*
D000606:Amino Sugars; D011134:Polysaccharides; D019087:Selectins; C066929:polylactosamine; C106501:N-acetylglucosaminyltransferase IGnT; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase