Possible application of milk oligosaccharides for drug development.
By applying a finger-printing method to the analysis of human milk oligosaccharides, several oligosacchartides were found to be deleted in the milk of non-secretor or Lewis negative individual. This finding afforded a clue to elucidate the enzymatic basis of blood types in humans. Furthermore, disappearance of some major oligosaccharides led to the finding of five novel minor oligosaccharides, which were hidden under the major oligosaccharides. Later on, structures of more than seventy oligosaccharides were elucidated. These oligosaccharides are derived from eleven core oligosaccharides by sialylation and/or fucosylation. All these oligosaccharides contain lactose at their reducing termini. This evidence, together with the deletion phenomena found in the milk of two blood type individuals, suggested that the oligosaccharides are formed by the concerted action of glycosyltransferases, which are responsible for formation of the sugar chains of glycoproteins on the surface of epithelial cells constructing the mucous membrane. The elongation may start by the action of iGnT. This enzyme is responsible for the addition of a beta-N-acetylglucosamine residue to the C-3 position of the galactose moiety constructing the N-acetyllactosamine group of the sugar chains of glycoconjugates. Therefore, oligosaccharides in human milk may include many structures, starting from the N-acetyllactosamine residues in the sugar chains of various glycoproteins. Many evidences, which indicate that virulent enteric bacteria and viruses start their infection by binding to particular sugar chains of glycoconjugates on the surface of their target cells, were presented recently. Therefore, milk oligosaccharides are expected to be useful to inhibit the infection of these bacteria and viruses.
Kobata
Akira
A
Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. akobata@mx5.ttcn.ne.jp
D000017:ABO Blood-Group System; D015195:Drug Design; D006801:Humans; D007983:Lewis Blood Group Antigens; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000032:analysis / Q000737:chemistry / Q000627:therapeutic use*
D000017:ABO Blood-Group System; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides