合聚醇是一种新型的抗血栓剂,对醇异构酶具有广泛的活性
Moua Yang1, Ivan Hancco Zirena2, Quinn P Kennedy3
1Bloodworks Northwest Research Institute, Seattle, Washington, USA; Division of Hematology and Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA; Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
合聚醇,像PGHG一样,抑制蛋白质二硫化异构酶 (PDI) 和SARS-CoV-2 Mpro,作为抗血栓剂. 这些化合物对硫醇异构酶和SARS-CoV-2具有广泛的活性,影响病毒复制和血栓形成.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 蛋白质二硫化异构酶 (PDI) 和SARS-CoV-2主要蛋白质酶 (Mpro) 分享活性部位的囊蛋白,这对它们的功能至关重要.
- 反氧活性化合物可能会干扰这些酶,潜在地抑制病毒复制和血栓形成.
研究的目的:
- 确定SARS-CoV-2的植物化学抑制剂 Mpro.
- 确定这些抑制剂是否也阻断了醇异构酶.
- 评估已识别的化合物的抗血栓潜力.
主要方法:
- 使用PDI,ERp57,ERp5,ERp46和PDI突变体进行酶活性测定,以测试化聚醇.
- 血栓形成的体外和体外模型 (激光损伤,铁化物,尾巴切割试验) 以评估抗血栓和静血作用.
主要成果:
- 皮诺森布林7-O-(3''-加-4'',6''-(S) - 六基基基) -β-D-葡萄糖 (PGHG) 抑制了PDI和SARS-CoV-2 Mpro,在催化领域起作用.
- PGHG表现出各种醇异构酶的广泛抑制,其中烯基部分是活性的关键.
- 在小鼠模型中,PGHG和punicalagin表现出抗血栓作用.
结论:
- 合聚醇构成一种重要的抗血栓剂类.
- 这些化合物表现出广泛的醇异构酶抑制.
- 许多化聚也抑制了SARS-CoV-2 Mpro,这表明抗病毒应用的潜力.
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