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Updated: May 25, 2025

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
Colon-Targeting Supersulfide Donor-Drug Conjugates Align Forces against Inflammation
Yu Zhang1, Gao-Yao Cao1, Zhihao Zhou1
1Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing, Jiangsu 210009, China.
Abstract:
Supersulfides are rising stars in regulating redox. Their distinctive redox biological functions are becoming increasingly evident with the advancement of supersulfide donors. However, most existing donors are limited to releasing hydropersulfide (RSSH) only, and in addition, there is still a knowledge gap in translating supersulfides into therapeutic molecules. To this end, in this work, we devised and synthesized a supersulfide donor-drug conjugate, RSSS, containing an azo moiety. This bifunctional prodrug enables the production of hydrotrisulfide (RSSSH) catalyzed by intestinal azoreductase, accompanied by the release of the anti-inflammatory molecule 5-aminosalicylic acid (ASA). Notably, the corelease of the supersulfides with ASA exhibited colonic-targeting attributes, thereby synergistically contributing to the potent anti-inflammatory and antioxidant activities observed in cellular and animal models. This prodrug design is worthy of further development and translation in donor development and disease treatment.
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