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通过TRADD-TRAF2复杂接口评估选的心血管疾病的皮模仿剂

A Manikandan¹, S Jeevitha², Laharika Vusa¹

¹Dept. of Microbiology, M.S. Ramaiah College of Arts, Science and Commerce, Bengaluru, 560054 India.

In silico pharmacology

|October 30, 2023

概括

研究人员开发了新型的类药物来对抗动脉样硬化,一种心血管疾病. 这些化合物向TRADD-TRAF2相互作用,对疾病进展至关重要,提供了一种新的治疗途径.

科学领域:

生物化学和分子生物学
心血管疾病研究研究
药物发现和开发药物发现和开发

背景情况:

动脉样硬化 (AS) 是一种严重的心血管疾病 (CVD),由TRADD-TRAF2蛋白相互作用加剧.
这种相互作用激活NF-κB,通过可诱导的氧化合成酶 (iNOS) 产生氧化 (NO),促进AS.
针对TRADD-TRAF2接口为AS提供了一个潜在的治疗策略.

研究的目的:

选和开发皮多米米药物作为动脉样硬化的潜在治疗方法.
设计针对TRADD和TRAF2.2之间关键蛋白质蛋白相互作用的抑制剂.
为了确定可用于临床前评估的可用于药物治疗的模仿性化合物.

主要方法:

基于TRADD-TRAF2相互作用接口 (PDB ID: 1F3V) 的抑制性的化设计.
使用alanine扫描和使用pepMMsMIMIC虚拟选进行类优化.
分子对接,分子动力学 (MD) 模拟,密度函数理论 (DFT) 和ADMET预测用于化合物验证.

主要成果:

确定了三种具有强大的TRAF2结合的抑制 (MIP11-25L,MIP131-143h,MIP149-164m).
产生并选了大约600种类药物,确定了有前途的候选药物.
两种类药物MMs03918858和MMs03927281表现出高的结合亲和度 (分别为9.6和9.1千卡/mol).

结论:

针对TRADD-TRAF2相互作用的型模拟剂是动脉样硬化的可行的治疗候选药物.
MMs03918858和MMs03927281显示出基于结合能和可药性预测的显著潜力.
这些化合物被推用于进一步的临床前研究,以评估它们在治疗动脉样硬化的有效性.

关键词:

接收人接收人氨酸扫描扫描使用动脉样硬化是一种动脉样硬化.在CVD中,CVD是非常重要的.类模拟剂类模拟剂类模拟剂

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