title: Time-Gated Detection of Cystathionine γ-Lyase Activity and Inhibition with a Selective, Luminogenic Hydrogen Sulfide Sensor.
abstract: Herein, we report the design, synthesis, and characterization of a lanthanideIIIcomplex-based probe for the time-gated luminescence detection of hydrogen sulfide (H2S) in aqueous media. The probe's unique sensing mechanism relies on the selective reduction of azide to amine by sulfide, followed by intramolecular cyclization to form a quinolinone. The quinolinone is a sensitizer that absorbs near-UV light and transfers excitation energy to coordinated TbIIIor EuIIIions to trigger a strong "turn-on" luminescence response with ms-scale lifetimes characteristic of lanthanide complexes. Using this probe, we developed a robust, high throughput screening (HTS) assay for detecting H2S generated by cystathionine γ-lyase (CSE), one of the main producers of H2S in mammalian cells. In a 240-compound screen to identify potential CSE inhibitors, the EuIIIanalogue of the sensor showed a low false-positive rate and high Z'-factor (>0.7).
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor Street, MC 111, Chicago, Illinois, 60607, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor Street, MC 111, Chicago, Illinois, 60607, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UICentre for Drug Discovery, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UICentre for Drug Discovery, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
authors.forename: Atul D
authors.initials: AD
authors.lastname: Jain
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UICentre for Drug Discovery, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
authors.forename: Kiira
authors.initials: K
authors.lastname: Ratia
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UICentre for Drug Discovery, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
authors.forename: Gregory R J
authors.initials: GR
authors.lastname: Thatcher
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, UICentre for Drug Discovery, University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, Illinois, 60612, USA.
authors.forename: Terry W
authors.initials: TW
authors.lastname: Moore
authors.affiliation: Institute of Next Generation Matter Transformation, College of Chemical Engineering, Huaqiao University, 668 Jimei Blvd. Xiamen, Fujian, 361021, P. R. China.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Driver
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 W. Taylor Street, MC 111, Chicago, Illinois, 60607, USA.
authors.forename: Lawrence W
authors.identifier: http://orcid.org/0000-0003-4501-9357
authors.initials: LW
authors.lastname: Miller
mesh_terms: D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005063:Europium / Q000737:chemistry; D057166:High-Throughput Screening Assays; D006862:Hydrogen Sulfide / Q000032:analysis* / Q000737:chemistry; D028581:Lanthanoid Series Elements / Q000737:chemistry; D049408:Luminescent Agents / Q000138:chemical synthesis / Q000737:chemistry; D008163:Luminescent Measurements; D009682:Magnetic Resonance Spectroscopy
chemical_list: D028581:Lanthanoid Series Elements; D049408:Luminescent Agents; D005063:Europium; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide
keywords: high-throughput screening; hydrogen sulfide; lanthanides; luminescence; sensors