title: One-pot multi-enzyme (OPME) chemoenzymatic synthesis of sialyl-Tn-MUC1 and sialyl-T-MUC1 glycopeptides containing natural or non-natural sialic acid.
abstract: A series of STn-MUC1 and ST-MUC1 glycopeptides containing naturally occurring and non-natural sialic acids have been chemoenzymatically synthesized from Tn-MUC1 glycopeptide using one-pot multienzyme (OPME) approaches. In situ generation of the sialyltransferase donor cytidine 5'-monophosphate-sialic acid (CMP-Sia) using a CMP-sialic acid synthetase in the presence of an extra amount of cytidine 5'-triphosphate (CTP) and removal of CMP from the reaction mixture by flash C18 cartridge purification allow the complete consumption of Tn-MUC1 glycopeptide for quantitative synthesis of STn-MUC1. A Campylobacter jejuni β1-3GalT (CjCgtBΔ30-His6) mutant has been found to catalyze the transfer of one or more galactose residues to Tn-MUC1 for the synthesis of T-MUC1 and galactosylated T-MUC1. Sialylation of T-MUC1 using Pasteurella multocida α2-3-sialyltransferase 3 (PmST3) with Neisseria meningitidis CMP-sialic acid synthetase (NmCSS) and Escherichia coli sialic acid aldolase in one pot produced ST-MUC1 efficiently. These glycopeptides are potential cancer vaccine candidates.
authors.affiliation: Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Malekan
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fung
authors.forename: Vireak
authors.initials: V
authors.lastname: Thon
authors.forename: Zahra
authors.initials: Z
authors.lastname: Khedri
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Jingyao
authors.initials: J
authors.lastname: Qu
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000957:Antigens, Viral, Tumor / Q000737:chemistry; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D016123:Campylobacter jejuni / Q000201:enzymology; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology; D006020:Glycopeptides / Q000096:biosynthesis* / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000201:enzymology; D007652:Oxo-Acid-Lyases / Q000235:genetics / Q000378:metabolism; D016979:Pasteurella multocida / Q000201:enzymology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012794:Sialic Acids / Q000737:chemistry*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor; D001426:Bacterial Proteins; D006020:Glycopeptides; D011993:Recombinant Fusion Proteins; D012794:Sialic Acids; C586445:sialyl-Tn-MUC1; D012799:Sialyltransferases; C029156:N-acetyllactosaminide alpha-2,3-sialyltransferase; C018730:N-acetylneuraminate synthase; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase
keywords: Carbohydrate; Chemoenzymatic synthesis; Enzymatic synthesis; Glycopeptide; ST antigen; STn antigen; T antigen; Tn antigen
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