Targeted Delivery of Persulfides to the Gut: Effects on the Microbiome. Issue 11 (29th January 2021)

• Record Type: Journal Article
• Authors: Dillon, Kearsley M.; Morrison, Holly A.; Powell, Chadwick R.; Carrazzone, Ryan J.; Ringel‐Scaia, Veronica M.; Winckler, Ethan W.; Council‐Troche, R. McAlister; Allen, Irving C.; Matson, John B.
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 11(2021)
• Page Start: 6061
• Page End: 6067
• Publication Date: 2021-01-29
• Subjects: drug delivery -- inflammation -- microbiome -- oxidative stress -- stimuli responsiveness; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202014052
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Persulfides (R−SSH) have been hypothesized as potent redox modulators and signaling compounds. Reported herein is the synthesis, characterization, and in vivo evaluation of a persulfide donor that releases N ‐acetyl cysteine persulfide (NAC‐SSH) in response to the prokaryote‐specific enzyme nitroreductase. The donor, termed NDP‐NAC, decomposed in response to E. coli nitroreductase, resulting in release of NAC‐SSH. NDP‐NAC elicited gastroprotective effects in mice that were not observed in animals treated with control compounds incapable of persulfide release or in animals treated with Na2 S. NDP‐NAC induced these effects by the upregulation of beneficial small‐ and medium‐chain fatty acids and through increasing growth of Turicibacter sanguinis, a beneficial gut bacterium. It also decreased the populations of Synergistales bacteria, opportunistic pathogens implicated in gastrointestinal infections. This study reveals the possibility of maintaining gut health or treating microbiome‐related diseases by the targeted delivery of reactive sulfur species. Abstract : The persulfide donor NDP‐NAC (see structure) was synthesized and found to decompose in response to E. coli nitroreductase with the release of N ‐acetyl cysteine persulfide (NAC‐SSH). NDP‐NAC elicited gastroprotective effects in mice by the upregulation of beneficial small‐ and medium‐chain fatty acids, by increasing growth of Turicibacter sanguinis, a beneficial gut bacterium, and by decreasing populations of pathogenic Synergistales bacteria.