氨酸通过向NF-κB信号通路中的p65亚单元来表现出抗炎作用
Lu Tong1, Meng-Li Zha1, Junchi Hu2
1The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.
European journal of medicinal chemistry
|October 9, 2024
概括
一种天然化合物阿南丁 (adenanthin) 协同修饰p65 (RelA),以抑制NF-κB通路,从而揭示了它的抗炎机制. 这一发现有助于开发新的炎症和癌症治疗方法.
科学领域:
- 自然产品化学 自然产品化学
- 分子药理学分子药理学
- 药用化学 医学化学
背景情况:
- 亚第南丁是拉布多西亚亚第南塔 (Rabdosia adenantha) 中的一种双类,具有抗癌和抗炎性质.
- 亚德南丁抗炎作用背后的精确分子机制尚不清楚.
- 电友性天然产品通常通过对蛋白质标的共价改性来发挥生物活性.
研究的目的:
- 用一种基于亲和力的新型无标签蛋白质分析 (ALFPP) 方法来识别阿德南丁的共价蛋白质标.
- 阐明阿德南丁发挥抗炎作用的分子机制.
- 探索阿德南丁在炎症和癌症治疗方面的潜力.
主要方法:
- 基于亲缘关系的无标签蛋白质分析 (ALFPP) 的开发和应用,用于目标识别.
- 利用LC-MS/MS,分子对接,电泳性移动性转移试验 (EMSA) 和基因组编辑进行机械研究.
- 研究了由腺氨丁对已识别的蛋白质标的共价修饰.
主要成果:
- ALFPP确定了27个潜在的共价标的腺素,包括p65 (RelA).
- 证明阿南丁对p65.5的Cys38残留物进行共价性修改.
- 表明这种修饰抑制了DNA与p65的结合,从而抑制了NF-κB信号通路.
结论:
- 亚第南丁通过通过p65修饰共同抑制NF-κB信号通路来发挥其抗炎活性.
- ALFPP是一种有效的工具,用于识别电友性天然产品的目标,特别是那些具有α,β不和基因组的产品.
- 阐明腺素的机制为其在治疗炎症性疾病和癌症方面的潜在临床应用提供了基础.
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