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通过衰老细胞敏感的生物对等的四素结合启动的衰老

Mengyang Chang¹, Yue Dong², Hang Xu²

¹Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, 85721, USA.

Angewandte Chemie (International ed. in English)

|January 17, 2024

概括

研究人员开发了一种新型的老化策略,使用生物对角四链接来选择性地消除老化的细胞. 这种方法可以为衰老和癌症干预提供有针对性的化疗药物和向蛋白质分解的仿真体 (PROTACs).

科学领域:

生物化学生物化学
细胞生物学细胞生物学
药物发现药物发现药物发现

背景情况:

衰老细胞清除显示出减缓衰老和增强癌症化疗的潜力.
开发有效的老龄化药物仍然是治疗研究中的一个重大挑战.

研究的目的:

建立一个使用老化细胞敏感生物对等四链接的老化策略.
为了证明选择性检测和消除衰老细胞.
探索这种策略的应用,以向蛋白质溶解向仿真体 (PROTACs) 作为老化剂的有针对性输送.

主要方法:

一种与银河糖 (Gal) 部分 (Gal-Tz) 相关的二甲 (Tz) 被设计为识别与衰老相关的β-银河糖酶.
-Tz促进了光探针和 doxorubicin 从中的前药物中点击释放.
该策略适应了PROTAC前药物TCO-ARV-771的选择性激活和输送,以诱导含odomain的蛋白质4的降解.

主要成果:

该Gal-Tz系统实现了高效的检测和消除老化的HeLa和A549细胞,老化指数为16.44.
成功地证明了PROTACs的选择性激活和传递到衰老细胞中.
该方法显示,在衰老细胞中选择性诱导含有odomain的蛋白4降解.

结论:

生物 orthogonal tetrazine 结合是一种选择性去除衰老细胞的可行策略.
这种方法为向老化疗法提供了一种有前途的方法,包括使用PROTACs.
这些发现为针对衰老和疾病中的细胞衰老的新干预措施铺平了道路.

关键词:

生物对等化学的化学.一个药物产品.衰老是一种衰老.年老的药物.氨酸的点击释放式释放.

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