One-pot multi-enzyme (OPME) chemoenzymatic synthesis of sialyl-Tn-MUC1 and sialyl-T-MUC1 glycopeptides containing natural or non-natural sialic acid

Hamed Malekan, Gabriel Fung, Vireak Thon, Zahra Khedri, Hai Yu, Jingyao Qu, Yanhong Li, Li Ding, Kit Lam, Xi Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4778-4785
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number16
DOIs
StatePublished - Aug 15 2013

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Glycopeptides
N-Acetylneuraminic Acid
N-Acylneuraminate Cytidylyltransferase
Sialyltransferases
Cytidine Monophosphate
Cytidine
Enzymes
N-acetylneuraminate lyase
Sialic Acids
Cytidine Triphosphate
Pasteurella multocida
Cancer Vaccines
Campylobacter jejuni
Neisseria meningitidis
Galactose
Escherichia coli
Purification
sialyl-Tn-MUC1

Keywords

  • Carbohydrate
  • Chemoenzymatic synthesis
  • Enzymatic synthesis
  • Glycopeptide
  • ST antigen
  • STn antigen
  • T antigen
  • Tn antigen

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

One-pot multi-enzyme (OPME) chemoenzymatic synthesis of sialyl-Tn-MUC1 and sialyl-T-MUC1 glycopeptides containing natural or non-natural sialic acid. / Malekan, Hamed; Fung, Gabriel; Thon, Vireak; Khedri, Zahra; Yu, Hai; Qu, Jingyao; Li, Yanhong; Ding, Li; Lam, Kit; Chen, Xi.

In: Bioorganic and Medicinal Chemistry, Vol. 21, No. 16, 15.08.2013, p. 4778-4785.

Research output: Contribution to journalArticle

Malekan, Hamed ; Fung, Gabriel ; Thon, Vireak ; Khedri, Zahra ; Yu, Hai ; Qu, Jingyao ; Li, Yanhong ; Ding, Li ; Lam, Kit ; Chen, Xi. / One-pot multi-enzyme (OPME) chemoenzymatic synthesis of sialyl-Tn-MUC1 and sialyl-T-MUC1 glycopeptides containing natural or non-natural sialic acid. In: Bioorganic and Medicinal Chemistry. 2013 ; Vol. 21, No. 16. pp. 4778-4785.
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AU - Fung, Gabriel

AU - Thon, Vireak

AU - Khedri, Zahra

AU - Yu, Hai

AU - Qu, Jingyao

AU - Li, Yanhong

AU - Ding, Li

AU - Lam, Kit

AU - Chen, Xi

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AB - 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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