Department of Chemistry, UCL, Christopher Ingold Building, 20, Gordon Street, London WC1H 0AJ, UK.
Department of Structural and Molecular Biology, UCL, Gower Street, London WC1E 6BT, UK.
Bioorg Med Chem. 2020 Nov 15;28(22):115740. doi: 10.1016/j.bmc.2020.115740. Epub 2020 Sep 5.
Coenzyme A (CoA) is a highly selective inhibitor of the mitotic regulatory enzyme Aurora A kinase, with a novel mode of action. Herein we report the design and synthesis of analogues of CoA as inhibitors of Aurora A kinase. We have designed and synthesised modified CoA structures as potential inhibitors, combining dicarbonyl mimics of the pyrophosphate group with a conserved adenosine headgroup and different length pantetheine-based tail groups. An analogue with a -SH group at the end of the pantotheinate tail showed the best IC50, probably due to the formation of a covalent bond with Aurora A kinase Cys290.
辅酶 A（CoA）是一种高度选择性的有丝分裂调节酶 Aurora A 激酶抑制剂，具有新颖的作用模式。本文报道了作为 Aurora A 激酶抑制剂的 CoA 类似物的设计与合成。我们设计并合成了经过修饰的 CoA 结构作为潜在抑制剂，将焦磷酸盐基团的二羰基模拟物与保守的腺苷头部基团和不同长度的泛酰巯基乙胺基尾部基团结合在一起。在泛酰巯基乙胺基尾部末端带有 -SH 基团的类似物表现出最佳的 IC50，这可能是由于与 Aurora A 激酶 Cys290 形成了共价键。
