title: Sialyltransferase inhibition and recent advances.
abstract: Sialic acids, existing as terminal sugars of glycoconjugates, play important roles in various physiological and pathological processes, such as cell-cell adhesion, immune defense, tumor cell metastasis, and inflammation. Sialyltransferases (STs) catalyze the transfer of sialic acid residues to non-reducing oligosaccharide chains of proteins and lipids, using cytidine monophosphate N-acetylneuraminic acid (CMP-Neu5Ac) as the donor. Elevated sialyltransferase activity leads to overexpression of cell surface sialic acids and contributes to many disease developments, such as cancer and inflammation. Therefore, sialyltransferases are considered as potential drug targets for disease treatment. Inhibitors of sialyltransferases thus are of medicinal interest, especially for the cancer therapy. In addition, sialyltransferase inhibitors are useful tool to study sialyltransferase function and related mechanisms. This review highlights recent development of inhibitors of sialyltransferases reported since 2004. The inhibitors are summarized as eight groups: 1) sialic acid analogs, 2) CMP-sialic acid analogs, 3) cytidine analogs, 4) oligosaccharide derivatives, 5) aromatic compounds, 6) flavonoids, 7) lithocholic acid analogs, and 8) others. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.
authors.affiliation: College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China. Electronic address: wanglibo66@sina.com.
authors.forename: Libo
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Chemical and Biomedical Engineering and Center for Gene Regulation in Health and Disease (GRHD), Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, United States. Electronic address: x.sun55@csuohio.edu.
authors.forename: Xue-Long
authors.initials: XL
authors.lastname: Sun
mesh_terms: D055162:Biocatalysis; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D015394:Molecular Structure; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid
keywords: CMP-sialic acid; Fluorinated sialic acid; Polysialyltransferases; Sialic acids; Sialylation; Sialyltransferases