Sialyltransferase inhibition and recent advances.

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.

Wang L ，Liu Y ，Wu L ，Sun XL ... -  《-》

Sialyltransferases with enhanced legionaminic acid transferase activity for the preparation of analogs of sialoglycoconjugates.

Legionaminic acids (Leg) are bacterial analogs of neuraminic acid, with the same stereochemistry but different substituents at C5, C7 and C9. Hence they may be incorporated into useful analogs of sialoglycoconjugates, and we previously reported two sialyltransferases that could utilize cytidine monophosphate (CMP)-Leg5Ac7Ac for preparation of Leg glycoconjugates, which were resistant to sialidases [Watson DC, Leclerc S, Wakarchuk WW, Young NM. 2011. Enzymatic synthesis and properties of glycoconjugates with legionaminic acid as a replacement for neuraminic acid. Glycobiology. 21:99-108.]. These were the porcine ST3Gal1 and Pasteurella multocida sialyltransferases. We now report two additional sialyltransferases with superior Leg-transferase properties to the previous two. These are (i) a truncated form of a Photobacterium α2,6-sialyltransferase with an Ala-Met mutation in its active site, and (ii) an α2,3-sialyltransferase from Neisseria meningitidis MC58 with a higher transferase activity than the P. multocida enzyme, with either CMP-Neu5Ac or CMP-Leg5Ac7Ac as the donor. These enzymes will enable the production of useful Leg5Ac7Ac glycoconjugate derivatives with either α2,6 or α2,3 linkages and unique biological properties.

Watson DC ，Wakarchuk WW ，Leclerc S ，Schur MJ ，Schoenhofen IC ，Young NM ，Gilbert M ... -  《-》

Synthesis of CMP-9''-modified-sialic acids as donor substrate analogues for mammalian and bacterial sialyltransferases.

Kajihara Y ，Kamitani T ，Sato R ，Kamei N ，Miyazaki T ，Okamoto R ，Sakakibara T ，Tsuji T ，Yamamoto T ... -  《CARBOHYDRATE RESEARCH》

Structural Basis for Binding of Fluorescent CMP-Neu5Ac Mimetics to Enzymes of the Human ST8Sia Family.

Volkers G ，Lizak C ，Niesser J ，Rosell FI ，Preidl J ，Gnanapragassam VS ，Horstkorte R ，Rademann J ，Strynadka NCJ ... -  《-》

Synthesis of a fluorescently tagged sialic acid analogue useful for live-cell imaging.

Suzuki K ，Ohtake A ，Ito Y ，Kanie O ... -  《-》