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  Total synthesis of dansylated Park's nucleotide for high-throughput MraY assays.

Wohnig, S., Anatol, P. S. A., Koppermann, S., Mieskes, G., Gisch, N., Jahn, R., et al. (2016). Total synthesis of dansylated Park's nucleotide for high-throughput MraY assays. Chemistry - A European Journal, 22(49), 17813-17819. doi:10.1002/chem.201604279.

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 Creators:
Wohnig, S., Author
Anatol, P. S. A., Author
Koppermann, S., Author
Mieskes, G.1, Author           
Gisch, N., Author
Jahn, R.1, Author           
Ducho, C., Author
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              

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Free keywords: Antibiotics; Enzyme assays; Fluorescence; Medicinal chemistry; Peptidoglycan
 Abstract: 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.

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Language(s): eng - English
 Dates: 2016-10-282016-12-05
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/chem.201604279
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Title: Chemistry - A European Journal
Source Genre: Journal
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Pages: - Volume / Issue: 22 (49) Sequence Number: - Start / End Page: 17813 - 17819 Identifier: -