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Total Synthesis of Dansylated Park's Nucleotide for High‐Throughput MraY Assays
Author(s) -
Wohnig Stephanie,
Spork Anatol P.,
Koppermann Stefan,
Mieskes Gottfried,
Gisch Nicolas,
Jahn Reinhard,
Ducho Christian
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604279
Subject(s) - translocase , high throughput screening , nucleotide , biochemistry , chemistry , substrate (aquarium) , peptidoglycan , bacteria , enzyme , biology , gene , genetics , ecology , chromosomal translocation
The membrane protein translocase I (MraY) is a key enzyme in bacterial peptidoglycan biosynthesis. It is therefore frequently discussed as a target for the development of novel antibiotics. The screening of compound libraries for the identification of MraY inhibitors is enabled by an established fluorescence‐based MraY assay. However, this assay requires a dansylated derivative of the bacterial biosynthetic intermediate Park's nucleotide as the MraY substrate. Isolation of Park's nucleotide from bacteria and subsequent dansylation only furnishes limited amounts of this substrate, thus hampering the high‐throughput screening for MraY inhibitors. Accordingly, the efficient provision of dansylated Park's nucleotide is a major bottleneck in the exploration of this promising drug target. In this work, we present the first total synthesis of dansylated Park's nucleotide, affording an unprecedented amount of the target compound for high‐throughput MraY assays.