Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
Department of Biochemistry, Stellenbosch University, Stellenbosch 7600, South Africa.
Bioorg Med Chem. 2018 Dec 1;26(22):5896-5902. doi: 10.1016/j.bmc.2018.10.042. Epub 2018 Nov 2.
Pantothenate kinase (PanK) catalyzes the transformation of pantothenate to 4'-phosphopantothenate, the first committed step in coenzyme A biosynthesis. While numerous pantothenate antimetabolites and PanK inhibitors have been reported for bacterial type I and type II PanKs, only a few weak inhibitors are known for bacterial type III PanK enzymes. Here, a series of pantothenate analogues were synthesized using convenient synthetic methodology. The compounds were exploited as small organic probes to compare the ligand preferences of the three different types of bacterial PanK. Overall, several new inhibitors and substrates were identified for each type of PanK.
泛酸激酶（PanK）催化泛酸转化为 4'-磷酸泛酸，这是辅酶 A 生物合成的第一步。虽然已经报道了许多细菌 I 型和 II 型 PanK 的泛酸抗代谢物和 PanK 抑制剂，但仅知道少数针对细菌 III 型 PanK 酶的弱抑制剂。在这里，使用方便的合成方法合成了一系列泛酸类似物。这些化合物被用作小分子有机探针，以比较三种不同类型的细菌 PanK 的配体偏好。总的来说，每种 PanK 都鉴定出了几种新的抑制剂和底物。
