title: Chemoenzymatic synthesis of sialosides containing C7-modified sialic acids and their application in sialidase substrate specificity studies.
abstract: Modifications at the glycerol side chain of sialic acid in sialosides modulate their recognition by sialic acid-binding proteins and sialidases. However, limited work has been focused on the synthesis and functional studies of sialosides with C7-modified sialic acids. Here we report chemical synthesis of C4-modified ManNAc and mannose and their application as sialic acid precursors in a highly efficient one-pot three-enzyme system for chemoenzymatic synthesis of α2-3- and α2-6-linked sialyl para-nitrophenyl galactosides in which the C7-hydroxyl group in sialic acid (N-acetylneuraminic acid, Neu5Ac, or 2-keto-3-deoxynonulosonic acid, Kdn) was systematically substituted by -F, -OMe, -H, and -N3 groups. Substrate specificity study of bacterial and human sialidases using the obtained sialoside library containing C7-modified sialic acids showed that sialosides containing C7-deoxy Neu5Ac were selective substrates for all bacterial sialidases tested but not for human NEU2. The information obtained from sialidase substrate specificity can be used to guide the design of new inhibitors that are selective against bacterial sialidases.
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Khedri
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Saddam
authors.initials: S
authors.lastname: Muthana
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Musleh M
authors.initials: MM
authors.lastname: Muthana
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Hsiao
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA. Electronic address: xiichen@ucdavis.edu.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D001419:Bacteria / Q000201:enzymology; D060326:Chemistry Techniques, Synthetic; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012794:Sialic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D012794:Sialic Acids; D009439:Neuraminidase
keywords: C7-modified sialic acid; Chemoenzymatic synthesis; Sialidase; Sialoside; Sialyltransferase; Substrate specificity