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抑制剂的生物模拟设计以阻止CD47/SIRPα相互作用

Si Zheng¹, Yufan Ji¹, Nanxing Li¹

¹Department of Biochemical Engineering and Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, People's Republic of China.

Langmuir : the ACS journal of surfaces and colloids

|December 1, 2023

概括

研究人员确定了CD47在瘤细胞和SIRPα在巨细胞之间的关键相互作用. 一种新型的抑制剂ZLIRTLHEWY旨在阻止这种相互作用,通过增强对瘤的免疫反应来显示抗癌疗法的潜力.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
计算化学计算化学

背景情况:

CD47是瘤细胞上的一种蛋白质,通过结合巨细胞上的SIRPα来促进免疫逃避.
针对CD47-SIRPα相互作用是癌症免疫疗法的有希望的策略.

研究的目的:

分析CD47和人类SIRPα (V1和V2变体) 之间的分子相互作用.
为潜在的抗癌应用设计和验证针对CD47-SIRPα相互作用的抑制剂.

主要方法:

分子动力学 (MD) 模拟.分子动力学 (MD) 模拟.
分子力学Poisson-Boltzmann表面积 (MM-PBSA) 的计算.
类库设计,分子对接和实验验证.

主要成果:

疏水性相互作用是CD47-SIRPα结合的主要驱动力.
特定的CD47残留物 (Z1,L2,E35,Y37,E97,L101,T102) 显著有助于结合.
在8000名候选人中确定了一种高亲和性抑制剂ZLIRTLHEWY,它对SIRPα的两种变体都表现出强烈的结合.

结论:

鉴定到的抑制剂通过向CD47-SIRPα通路,显示出潜在的抗癌功能.
这项研究为开发抗癌新型免疫疗法提供了基础.

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