Synthesis, structural elucidation and biochemical analysis of immunoactive glucuronosyl diacylglycerides of Mycobacteria and Corynebacteria

Benjamin Cao, Xiangqiang Chen, Yoshiki Yamaryo, Mark B Richardson, Kirstee L Martin, G N Khairallah, Thusitha Wasantha Thilaka Rupasinghe, Roisin M O'Flaherty, Richard Alfred John O'Hair, Julie E Ralton, Paul Kaighin Crellin, Ross Leon Coppel, Malcolm J McConville, Spencer John Williams

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)


Glucuronosyl diacylglycerides (GlcAGroAc2) are functionally important glycolipids and membrane anchors for cell wall lipoglycans in the Corynebacteria. Here we describe the complete synthesis of distinct acyl-isoforms of GlcAGroAc2 bearing both acylation patterns of (R)-tuberculostearic acid (C19:0) and palmitic acid (C16:0) and their mass spectral characterization. Collision-induced fragmentation mass spectrometry identified characteristic fragment ions that were used to develop rules allowing the assignment of the acylation pattern as C19:0 (sn-1), C16:0 (sn-2) in the natural product from Mycobacterium smegmatis, and the structural assignment of related C18:1 (sn-1), C16:0 (sn-2) GlcAGroAc2 glycolipids from M. smegmatis and Corynebacterium glutamicum. A synthetic hydrophobic octyl glucuronoside was used to characterize the GDP-mannose-dependent mannosyltransferase MgtA from C. glutamicum that extends GlcAGroAc2. This enzyme is an Mg(2+)/Mn(2+)-dependent metalloenzyme that undergoes dramatic activation upon reduction with dithiothreitol.
Original languageEnglish
Pages (from-to)2175-2190
Number of pages16
JournalThe Journal of Organic Chemistry
Issue number6
Publication statusPublished - 2013

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