Development of fluorescent probes for detecting reactive sulfur species and their application to development of inhibitors for 3MST

Honami Echizen, Kenjiro Hanaoka

Research output: Contribution to journalArticlepeer-review

Abstract

Hydrogen sulfide (H2S) has been reported to play an important role in biological systems. More recently, sulfane sulfur (sulfur with 0 or −1 charge) molecules have been also reported to be involved in various biological phenomena such as regulation of redox signaling and antioxidant functions. Fluorescent probes are one of the important chemical tools because it is easy to use and enable the real-time detection of the target molecules in living cells and tissues. We have successfully developed a highly selective H2S-detecting fluorescent probe, HSip-1. HSip-1 has been designed on the basis of the facts that the macrocyclic polyamine ligands form a stable complex with Cu2+, and Cu2+ also reacts with H2S and make a stable CuS complex. SSip-1 is a fluorescent probe for detecting sulfane sulfur and this fluorescent probe is designed on the basis of the unique feature of sulfane sulfur to bind reversibly to other sulfur atoms and the intramolecular spirocyclization reaction of xanthene dyes. SSip-1 is a highly selective fluorescent probe and can detect sulfane sulfur reversibly. Both HSip-1 and SSip-1 were able to be used for the live-cell fluorescence imaging. Further, we applied HSip-1 to the high-throughput screening (HTS) for the inhibitors of 3-mercaptopyruvate sulfurtransferase (3MST), one of the reactive sulfur species (RSS)-generating enzymes. We successfully found new 3MST inhibitors by screening of 174,118 compounds. We expect that these fluorescent probes and inhibitors would be useful to elucidate new functions of RSS and RSS-generating enzymes.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalFolia Pharmacologica Japonica
Volume154
Issue number3
DOIs
Publication statusPublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

Fingerprint

Dive into the research topics of 'Development of fluorescent probes for detecting reactive sulfur species and their application to development of inhibitors for 3MST'. Together they form a unique fingerprint.

Cite this