双甲类似物抑制人类和老鼠的11β-基固醇脱酶1根据其脂友性
Hong Wang1,2,3,4, Jianmin Sang1,2,3, Zhongyao Ji1,2,3
1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
双甲 (BPA) 的类似物抑制了11β-基固醇脱酶1 (11β-HSD1) 酶. 脂性和分子性质决定了BPA模拟对人类和老鼠11β-HSD1.1.的抑制强度.
科学领域:
- 生物化学 生物化学
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
背景情况:
- 双甲 (BPA) 类似物在工业和消费品中普遍存在.
- BPA类似物对关键代谢酶11β-基固醇脱酶1 (11β-HSD1) 的影响尚不清楚.
研究的目的:
- 研究六种BPA类似物对人类和老鼠11β-HSD1.1的抑制作用.
- 阐明化学性质和抑制功效之间的关系.
主要方法:
- 对人类和老鼠的11β-HSD1.1进行了酶抑制试验.
- 分子对接被用来预测结合相互作用.
- 使用物理化学性质分析了定量结构-活性关系.
主要成果:
- 双H和双G表现出人类11β-HSD1最强的抑制作用 (IC50值分别为0.75μM和5.06μM).
- 与人类的11β-HSD1相比,大鼠11β-HSD1的抑制显著较弱.
- 所有测试的BPA类似物都作为混合/竞争性抑制剂起作用.
- 分子对接揭示了双H和G与Ser170在人类11β-HSD1活性部位的结相互作用.
- 抑制功效与脂性,分子量和体积相反相关,与结合能量相对正相关.
结论:
- 在11β-HSD1上,BPA类型的抑制强度受其脂性,分子量,重原子数,分子体积和结合亲和力的影响.
- 这些发现凸显了BPA类似物通过调节葡萄糖皮质类代谢来产生潜在的内分泌干扰作用.
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