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苯二氮翁离子的直接细胞内递送，如酪氨酸磷酸化增加所观察到的。

Direct Intracellular Delivery of Benzene Diazonium Ions As Observed by Increased Tyrosine Phosphorylation.

机构信息

Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United States.

Department of Medicine, Division of Endocrinology, University of Arizona College of Medicine, Tucson, Arizona 85721, United States.

出版信息

Biochemistry. 2022 Apr 19;61(8):656-664. doi: 10.1021/acs.biochem.1c00820. Epub 2022 Mar 18.

DOI:10.1021/acs.biochem.1c00820
PMID:35302352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9203130/
Abstract

A challenge within the field of bioconjugation is developing probes to uncover novel information on proteins and other biomolecules. Intracellular delivery of these probes offers the promise of giving relevant context to this information, and these probes can serve as hypothesis-generating tools within complex systems. Leveraging the utility of triazabutadiene chemistry, herein, we discuss the development of a probe that undergoes reduction-mediated deprotection to rapidly deliver a benzene diazonium ion (BDI) into cells. The intracellular BDI resulted in an increase in global tyrosine phosphorylation levels. Seeing phosphatase dysregulation as a potential source of this increase, a tyrosine phosphatase (PTP1B) was tested and shown to be both inhibited and covalently modified by the BDI. In addition to the expected azobenzene formation at tyrosine side chains, key reactive histidine residues were also modified.

摘要

生物共轭领域的一个挑战是开发探针，以揭示蛋白质和其他生物分子的新信息。这些探针的细胞内传递有望为这些信息提供相关背景，并且这些探针可以作为复杂系统中的假设生成工具。利用三氮杂丁二烯化学的实用性，本文讨论了一种探针的开发，该探针通过还原介导的脱保护作用迅速将苯重氮离子 (BDI) 递送到细胞中。细胞内的 BDI 导致整体酪氨酸磷酸化水平增加。由于发现磷酸酶失调可能是这种增加的潜在原因，因此测试了一种酪氨酸磷酸酶 (PTP1B)，并发现其被 BDI 抑制和共价修饰。除了在酪氨酸侧链上预期形成偶氮苯外，关键的反应性组氨酸残基也被修饰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/05e482c9f659/nihms-1813139-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/f2427c116a26/nihms-1813139-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/e6b759e65ed2/nihms-1813139-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/b5f22031ed5b/nihms-1813139-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/d3fd29404c23/nihms-1813139-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/366cef8890fc/nihms-1813139-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/05e482c9f659/nihms-1813139-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/f2427c116a26/nihms-1813139-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/e6b759e65ed2/nihms-1813139-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/b5f22031ed5b/nihms-1813139-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/d3fd29404c23/nihms-1813139-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/366cef8890fc/nihms-1813139-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b43/9203130/05e482c9f659/nihms-1813139-f0007.jpg

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