西北大学郭媛团队提出了构建精确跟踪衰老的智能荧光探针的二维设计策略。 相关研究成果于2021年2月24日发表在国际顶尖学术期刊《德国应用化学》。

细胞衰老的跟踪通常依赖于衰老相关的β-半乳糖苷酶（SA-β-gal）的检测。以前的SA‐β‐gal探针仅涉及一个维度：该酶在溶酶体中的积累。然而，这还不足以决定衰老细胞的命运，因为富含溶酶体的内源性β-半乳糖不仅与衰老有关，还与其他一些生理过程有关。

为了解决这个问题，研究人员引入了荧光探针，包括第二个维度：溶酶体pH，因为脱酸化是衰老细胞中溶酶体的一个独特特征。通过这种新颖的设计，该探针实现了对SA‐β‐gal与癌症相关β‐gal的出色区分，这使得它们能够更精确地跟踪细胞衰老和组织老化。

模型酶大肠杆菌β-半乳糖突变体（E537Q）与每个探针复合的晶体结构进一步揭示了探针识别的结构基础。

附：英文原文

Title: Two‐Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence

Author: Yuan Guo, Ying Gao, Yulu Hu, Qimeng Liu, Xiaokang Li, Xinming Li, Chu-Young Kim, Tony D. James, Jian Li, Xi Chen

Issue&Volume: 2021-02-24

Abstract: The tracking of cellular senescence usually depends on the detection of senescence‐associated β‐galactosidase (SA‐β‐gal). Previous probes for SA‐β‐gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous β‐gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de‐acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA‐β‐gal from cancer‐associated β‐gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme  E. coli  β‐gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.

DOI: 10.1002/anie.202101278

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202101278