TY - JOUR
T1 - Synthesis, structural elucidation and biochemical analysis of immunoactive glucuronosyl diacylglycerides of Mycobacteria and Corynebacteria
AU - Cao, Benjamin
AU - Chen, Xiangqiang
AU - Yamaryo, Yoshiki
AU - Richardson, Mark B
AU - Martin, Kirstee L
AU - Khairallah, G N
AU - Rupasinghe, Thusitha Wasantha Thilaka
AU - O'Flaherty, Roisin M
AU - O'Hair, Richard Alfred John
AU - Ralton, Julie E
AU - Crellin, Paul Kaighin
AU - Coppel, Ross Leon
AU - McConville, Malcolm J
AU - Williams, Spencer John
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://pubs.acs.org/doi/pdf/10.1021/jo302508e
U2 - 10.1021/jo302508e
DO - 10.1021/jo302508e
M3 - Article
VL - 78
SP - 2175
EP - 2190
JO - The Journal of Organic Chemistry
JF - The Journal of Organic Chemistry
SN - 0022-3263
IS - 6
ER -