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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

含有抗叶酸抑制剂的磷酸核糖焦磷酸酯氨基转移酶（PPAT）的硅胶结构模型和分子对接分析

卷 19, 期 5, 2019

页: [408 - 416] 页: 9

弟呕挨: 10.2174/1568009619666181127115015

价格: $65

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摘要

背景：癌症仍然是世界上最严重的疾病之一。强大的新陈代谢是癌症的标志。 PPAT（磷酸核糖焦磷酸酰胺转移酶）催化从头嘌呤生物合成的第一步。因此，PPAT是De novo嘌呤核苷酸生物合成中的关键调节点，是白血病和其他癌症治疗的有吸引力且可信的药物靶标。 目的：本研究对PPAT蛋白进行了详细的计算分析，PPAT蛋白是嘌呤生物合成的关键酶，受到许多叶酸衍生物的抑制，因此我们的目的是研究和评价抗叶酸衍生物的抑制作用; lomexterol（LTX）甲氨蝶呤（LTX）和pipretixin（PTX）与人PPAT有效捕获和抑制从头嘌呤生物合成途径。 方法：进行结构计算方法的序列，然后进行分子对接实验，以深入了解所选抗叶酸衍生物对PPAT重要结构特征的抑制模式，结合方向和结合亲和力。结果：结果表明抗叶酸抑制剂对PPAT分子的保守活性位点具有强亲和力，包括许多疏水性，氢键，范德华力和静电相互作用。 结论：最后，选择的抗叶酸抑制剂与人PPAT的强烈物理相互作用表明抗叶酸衍生物对癌症治疗的选择性抑制从头嘌呤生物合成途径。

关键词: 酰胺磷酸核糖基转移酶（PPAT），从头嘌呤生物合成抗叶酸，分子对接，癌症治疗，强力代谢，抗叶酸衍生物。

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