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- W2080478948 abstract "A new class of antibacterial agents for Gram-negative bacteria, rationally designed to inhibit the incorporation of 3-deoxy-D-manno-octulosonate into lipopolysaccharide (LPS), was recently reported. In Salmonella typhimurium, where the lipid A species are well characterised, it was previously demonstrated that the addition of a compound which inhibits the enzyme 3-deoxy-manno-octulosonate cytidylytransferase (CMP-KDO synthetase; EC 2.7.7.38) leads to rapid accumulation of lipid A derivatives. The major lipid A species, IV A (O-(2-amino-2-deoxy-β-D-glucopyranosyl)-(1-6)-2-amino-2-deoxy-α-D-glucose, acylated at positions 2, 3, 2′, 3′ with β-hydroxymyristoyl groups and bearing phosphates at positions 1 and 4′), was shown to be converted mainly to LPS by pulse-chase experiments in the absence of inhibitor. Labelled precursor (IV A ) was also chased to other more polar lipid A derivatives. During chase in the presence of inhibitor, there was no conversion to LPS, while the major lipid A species was converted to the same polar lipid A derivatives as in chase without inhibitor. Our data indicate that despite the accumulation of several species of lipid A derivatives during inhibition of LPS synthesis, only IV A is destined for synthesis of mature LPS when LPS synthesis resumes. The more polar lipid A derivatives would thus represent aberrant side reaction products which occur when the pathway is inhibited.Key words: CMP-KDO synthetase, lipopolysaccharide synthesis, lipid A precursor, 3-deoxy-D-manno-octulosonate analogs." @default.
- W2080478948 created "2016-06-24" @default.
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- W2080478948 date "1989-06-01" @default.
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- W2080478948 title "Accumulation of incomplete metabolic side products of lipid A in Salmonella typhimurium during inhibition of 3-deoxy-D-manno-octulosonate incorporation by a new class of antibacterial agents" @default.
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- W2080478948 doi "https://doi.org/10.1139/m89-104" @default.
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