title: Total Synthesis of Dansylated Park's Nucleotide for High-Throughput MraY Assays.
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.
authors: Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123, Saarbrücken, Germany.|Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
authors: Stephanie
authors: S
authors: Wohnig
authors: Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123, Saarbrücken, Germany.|Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.|Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany.
authors: Anatol P
authors: AP
authors: Spork
authors: Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123, Saarbrücken, Germany.|Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
authors: Stefan
authors: http://orcid.org/0000-0003-3905-4295
authors: S
authors: Koppermann
authors: Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany.
authors: Gottfried
authors: G
authors: Mieskes
authors: Division of Bioanalytical Chemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845, Borstel, Germany.
authors: Nicolas
authors: N
authors: Gisch
authors: Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany.
authors: Reinhard
authors: http://orcid.org/0000-0003-1542-3498
authors: R
authors: Jahn
authors: Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123, Saarbrücken, Germany.|Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077, Göttingen, Germany.
authors: Christian
authors: http://orcid.org/0000-0002-0629-9993
authors: C
authors: Ducho
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D009711:Nucleotides / Q000096:biosynthesis / Q000737:chemistry*; D014166:Transferases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009711:Nucleotides; D014166:Transferases
keywords: antibiotics; enzyme assays; fluorescence; medicinal chemistry; peptidoglycan