Department of Medicinal Chemistry, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5757-62. doi: 10.1016/j.bmcl.2010.07.139. Epub 2010 Aug 5.
The enzyme MurA performs an essential step in peptidoglycan biosynthesis and is therefore a target for the discovery of novel antibacterial compounds. We report here the inhibition of MurA by natural products from tulips (tulipalines and tuliposides), and the structure-activity relationships of various derivatives. The inhibition of MurA can be related to antibacterial activity, and MurA is probably one of the relevant molecular targets of the tulipaline derivatives. MurA inhibition by this class of compounds depends on the presence of the substrate UNAG, which indicates non-covalent suicide inhibition as observed previously for cnicin. With respect to selectivity, however, the reactivity against arbitrary sulfhydryl groups, such as in glutathione, could not yet be sufficiently separated from MurA inhibition in the present dataset.
酶 MurA 在肽聚糖生物合成中发挥重要作用，因此是发现新型抗菌化合物的目标。我们在这里报告了天然产物郁金香（郁金香碱和郁金香糖苷）对 MurA 的抑制作用，以及各种衍生物的结构-活性关系。MurA 的抑制作用与抗菌活性有关，MurA 可能是郁金香衍生物的相关分子靶标之一。该类化合物对 MurA 的抑制作用取决于底物 UNAG 的存在，这表明与先前观察到的 cnicin 一样，是非共价自杀抑制。然而，就选择性而言，在目前的数据集中，针对任意巯基（如谷胱甘肽）的反应性还不能与 MurA 抑制充分分离。
