Antigen 85C-mediated acyl-transfer between synthetic acyl donors and fragments of the arabinan

Aditya K. Sanki, Julie Boucau, Donald R. Ronning, Steven J. Sucheck

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Antigen 85 (ag85) is a complex of acyltransferases (ag85A-C) known to play a role in the mycolation of the d-arabino-d-galactan (AG) component of the mycobacterial cell wall. In order to better understand the chemistry and substrate specificity of ag85, a trehalose monomycolate mimic p-nitrophenyl 6-O-octanoyl-β-d-glucopyranoside (1) containing an octanoyl moiety in lieu of a mycolyl moiety was synthesized as an acyl donor. Arabinofuranoside acceptors, methyl α-d-arabinofuranoside (2), methyl β-d- arabinofuranoside (3), and methyl 2-O-β-d-arabinofuranosyl-α-d- arabinofuranoside (9) were synthesized to mimic the terminal saccharides found on the AG. The acyl transfer reaction between acyl donor 1 and acceptors 2, 3, and 9 in the presence of ag85C from Mycobacterium tuberculosis (M. tuberculosis) resulted in the formation of esters, methyl 2, 5-di-O-octanoyl-α-d- arabinofuranoside (10), methyl 5-O-octanoyl-β-d-arabinofuranoside (11), and methyl 2-O-(5-O-octanoyl-β-d-arabinofuranosyl)-5-O-octanoyl-α-d- arabinofuranoside (12) in 2 h, 2 h and 8 h, respectively. The initial velocities of the reactions were determined with a newly developed assay for acyltransferases. As expected, the regioselectivity corresponds to mycolylation patterns found at the terminus of the AG in M. tuberculosis. The study shows that d-arabinose-based derivatives are capable of acting as substrates for ag85C-mediated acyl-transfer and the acyl glycoside 1 can be used in lieu of TMM extracted from bacteria to study ag85-mediated acyl-transfer and inhibition leading to the better understanding of the ag85 protein class.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalGlycoconjugate Journal
Volume26
Issue number5
DOIs
StatePublished - Jul 2009

Keywords

  • Antigen 85 (ag85) complex
  • D-Arabino-d-galactan (AG)
  • Mycobacterium tuberculosis
  • TDM
  • TMM

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Antigen 85C-mediated acyl-transfer between synthetic acyl donors and fragments of the arabinan'. Together they form a unique fingerprint.

Cite this