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.
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Authors | Hamed Malekan, Gabriel Fung, Vireak Thon, Zahra Khedri, Hai Yu, Jingyao Qu, Yanhong Li, Li Ding, Kit S Lam, Xi Chen |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 21
Issue 16
Pg. 4778-85
(Aug 15 2013)
ISSN: 1464-3391 [Electronic] England |
PMID | 23535562
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antigens, Viral, Tumor
- Bacterial Proteins
- Glycopeptides
- Recombinant Fusion Proteins
- Sialic Acids
- sialyl-Tn-MUC1
- Sialyltransferases
- N-acetyllactosaminide alpha-2,3-sialyltransferase
- N-acetylneuraminate synthase
- Oxo-Acid-Lyases
- N-acetylneuraminate lyase
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Topics |
- Antigens, Viral, Tumor
(chemistry)
- Bacterial Proteins
(genetics, metabolism)
- Base Sequence
- Campylobacter jejuni
(enzymology)
- Cloning, Molecular
- Escherichia coli
(enzymology)
- Glycopeptides
(biosynthesis, chemistry)
- Molecular Sequence Data
- Mutation
- Neisseria meningitidis
(enzymology)
- Oxo-Acid-Lyases
(genetics, metabolism)
- Pasteurella multocida
(enzymology)
- Recombinant Fusion Proteins
(biosynthesis, genetics)
- Sialic Acids
(chemistry)
- Sialyltransferases
(genetics, metabolism)
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