Total Synthesis of Dansylated Park's Nucleotide for High-Throughput MraY Assays
Total Synthesis of Dansylated Park's Nucleotide for High-Throughput MraY Assays
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DOI：
10.1002/chem.201604279
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发表时间：
2016-12-05
影响因子：
4.3
通讯作者：
Ducho, Christian
中科院分区：
文献类型：
--
作者：
Wohnig, Stephanie;Anatol, P. Spork A.;Ducho, Christian
膜蛋白转位酶I（MraY）是细菌肽聚糖生物合成的关键酶。因此，它经常被讨论作为开发新抗生素的目标。用于鉴定MraY抑制剂的化合物文库的筛选通过建立的基于荧光的MraY测定来实现。然而，该测定需要细菌生物合成中间体Park核苷酸的丹磺酰化衍生物作为MraY底物。从细菌中分离Park's核苷酸和随后的丹磺酰化仅使有限量的这种底物脱乙酰化，从而阻碍了MraY抑制剂的高通量筛选。因此，有效地提供丹磺酰化的帕克核苷酸是探索这种有前途的药物靶点的主要瓶颈。在这项工作中，我们首次全合成了丹磺酰化Park's核苷酸，为高通量MraY检测提供了前所未有的量的目标化合物。
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.