Synthetic polyprenol-pyrophosphate linked oligosaccharides are efficient substrates for mycobacterial galactan biosynthetic enzymes

Organic & Biomolecular Chemistry
Xiaochao XueTodd L Lowary

Abstract

Mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce a complex cell wall that is critical for their survival. The largest structural component of the cell wall, the mycolyl-arabinogalactan-peptidoglycan complex, has at its core a galactan domain composed of d-galactofuranose residues. Mycobacterial galactan biosynthesis has been proposed to involve two glycosyltransferases, GlfT1 and GlfT2, which elongate polyprenol-pyrophosphate linked glycosyl acceptor substrates using UDP-galactofuranose as the donor substrate. We here report the first chemical synthesis of GlfT1 and GlfT2 acceptor substrates containing pyrophosphate and polyprenol moieties (compounds 3, 4, 22 and 23). The approach involves chemical synthesis of an oligosaccharide, subsequent phosphorylation at the reducing end and coupling to a polyprenol phosphate. These compounds were shown to be substrates for either GlfT1 (22 and 23) or GlfT2 (3 and 4) and all were substantially more active than the corresponding alkyl glycoside substrates reported previously. Mass spectrometric analysis of the products formed from the reaction of 3, 4, 22 and 23 with the respective cognate enzyme and UDP-galactofuranose provide additional evidence for the gala...Continue Reading

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Citations

May 22, 2019·Organic & Biomolecular Chemistry·Qiang LiuDmitri V Filippov
Jan 16, 2020·Antibiotics·Zuzana KonyarikováKatarína Mikušová

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Methods Mentioned

BETA
X-ray
glycosylation
NMR
acetylation
size exclusion column chromatography
reverse-phase chromatography
reverse-phase

Software Mentioned

Graph Pad PRISM
MassLynx
GraphPad

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