biostudies-literatureAggarwal TAmerican Cancer SocietyRutgers Cancer Institute of New JerseyNIBIB NIH HHSSteven A. Cox FoundationNCI NIH HHSNational Institute of Biomedical Imaging and Bioengineeringe202421936https://www.ebi.ac.uk/biostudies/studies/S-EPMC11914935biostudies-literatureUnknown64(12)Fluorescent light-up aptamer (FLAP) systems are promising (bio)sensing platforms that are genetically encodable. However, FLAP-mediated detection of each distinct target necessitates either in vitro selection or engineering of nucleic acid sequences. Furthermore, an aptamer that binds an inorganic target or a chemical species with a short lifetime is challenging to realize. Here, we describe a small-molecule approach that makes it possible for a single FLAP system to detect chemically unique, non-fluorogenic, and reactive inorganics. We developed functionalized pre-ligands of RNA aptamers that bind benzylidene imidazolinones (Baby Spinach, Broccolli, Squash). Reactive inorganics, hydrogen sulfide (H₂S/HS^-) and hydrogen peroxide (H₂O₂), can specifAngewandte Chemie (International ed. in English)A Small-Molecule Approach Enables RNA Aptamers to Function as Sensors for Reactive Inorganic Targets.PMC11914935R21 EB029548P30 CA072720P30CA072720EB029548Aggarwal TErguven HGuven HIzgu ECGutierrez BCho SWang LfalseA Small-Molecule Approach Enables RNA Aptamers to Function as Sensors for Reactive Inorganic Targets.Fluorescent light-up aptamer (FLAP) systems are promising (bio)sensing platforms that are genetically encodable. However, FLAP-mediated detection of each distinct target necessitates either in vitro selection or engineering of nucleic acid sequences. Furthermore, an aptamer that binds an inorganic target or a chemical species with a short lifetime is challenging to realize. Here, we describe a small-molecule approach that makes it possible for a single FLAP system to detect chemically unique, non-fluorogenic, and reactive inorganics. We developed functionalized pre-ligands of RNA aptamers that bind benzylidene imidazolinones (Baby Spinach, Broccolli, Squash). Reactive inorganics, hydrogen sulfide (H₂S/HS^-) and hydrogen peroxide (H₂O₂), can specif2025-01-01T00:00:00Z2025 Mar2026-06-01T19:01:14.408Z2025-04-04T03:02:12.352ZS-EPMC119149353966685810.1002/anie.202421936