Target identification and occupancy measurement of necrosis avid agent rhein using bioorthogonal chemistry-enabling probes.

Abstract

Necrosis is an important biomarker, which only occurs in pathological situations. Tracking of necrosis avid agents is of crucial importance toward understanding their mechanisms. Herein, we developed a modular probe strategy based on bioorthogonal copper-free click chemistry. Structural modification of rhein with transcyclooctene (TCO) led to the identification of rhein-TCO2 as the most active probe with specific necrosis affinity. In a systematic evaluation, the colocalization of rhein-TCO2 in the nucleus (exposed DNA and rRNA) of necrotic cells was observed. This work provides a foundation for the development of target-identified of rhein compounds, and binding to exposed DNA and rRNA may be an important target of rhein compounds in necrotic cells.

• Authors: Cuihua Jiang, Jian Zhang, Shihe Hu, Meng Gao, Dongjian Zhang, Nan Yao, Qiaomei Jin
• Journal: RSC advances (RSC Adv) Vol. 12 Issue 26 Pg. 16491-16495 (Jun 01 2022) ISSN: 2046-2069 [Electronic] England
• PMID: 35754899 (Publication Type: Journal Article)
• Copyright: This journal is © The Royal Society of Chemistry.