Sulfated oligosaccharides: new targets for drug development?
Sulfated oligosaccharides display an important role in biological processes. They bind proteins through interactions mediated by highly specific sequences (heparin - antithrombin, heparan sulfate - growth factors / herpes simplex virus) or by electrostatic interaction between sulfate groups and cationic sites of proteins. Sulfated oligosaccharides are involved in biological events as protein localisation at cell surfaces, the control of proteolysis, the modulation of the angiogenesis and metastasis of tumours, the oligomerisation of cell growth factors. Sulfated residues have been recently found in glycoproteins, as GlcNAc or Mannose in N-glycosidic chains of different sources: gp120 of HIV, the envelope glycoprotein of influenza virus, the cysteine protease of Trypanosoma cruzi. This paper reviews recent findings concerning the implication of sulfated sugars in carbohydrate - protein interactions, from glycosaminoglycans to glycosidic chains in proteins, and their potential application as new targets for drugs/vaccines/diagnosis developments will be discussed. New approaches for their detection and analysis (ESI-MS, MALDI, Molecular Imprinting) are presented.
Kovensky
José
J
Laboratoire des Glucides CNRS UMR 6219, Institut de Chimie de Picardie, Université de Picardie Jules Verne, 33 Rue Saint-Leu, 80039 Amiens, France. jose.kovensky@u-picardie.fr
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D054802:Molecular Imprinting; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D013463:Sulfuric Acid Esters / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D009844:Oligosaccharides; D013463:Sulfuric Acid Esters