A super sensitive fluorescent probe for imaging endogenous hydrogen sulfide in living cells.

Hydrogen sulfide (H2S) that typically performs biphasic biological functions in organisms plays an opposite role at the concentrations above or below normal level of the organism. Therefore, it is significant to develop a fluorescent probe with high sensitivity and selectivity and rapid response for the detection of hydrogen sulfide in vivo. The work describes the design and biological applications of a novel turn-on fluorescence probe SS-N3 in which the quinoline quaternary ammonium salt derivative is introduced as the fluorescent skeleton and azide is employed as the detection group of H2S. The probe SS-N3 shows strong fluorescence at 610 nm, as the azide group is reduced to an amino group by H2S. The probe SS-N3 shows high selectivity to H2S than other anions and some biological mercaptans, and strong anti-interference capacity. In addition, the probe SS-N3 exhibits little cytotoxicity, improved photostability and large Stokes shift (135 nm), as well as can be effectively used as an indicator of H2S level in living cells.

Design and development of selective competitive fluorescent ligands for the detection and visualization of Kv7.2/7.3 in vitro.

A series of specific and potent fluorescent ligands were developed for labelling and visualizing Kv7.2/7.3 based molecular rotation restriction. Probes 21b and 24a were found to be safe and convenient tools to detect and visualize Kv7.2/7.3 in live cells and mouse brain tissue.

Photosensitive and Photoswitchable TRPA1 Agonists Optically Control Pain through Channel Desensitization.

Transient receptor potential ankyrin 1 (TRPA1) channel, as a nonselective ligand-gated cation channel robustly in dorsal root ganglion sensory neurons, is implicated in sensing noxious stimuli and nociceptive signaling. However, small-molecule tools targeting TRPA1 lack temporal and spatial resolution, limiting their use for validation of TRPA1 as a therapeutic target for pain. In our previous work, we found that 4,4'-(diazene-1,2-diyl)dianiline (AB1) is a photoswitchable TRPA1 agonist, but the poor water solubility and activity hinder its further development. Here, we report a series of specific and potent azobenzene-derived photoswitchable TRPA1 agonists (series 1 and 2) that enable optical control of the TRPA1 channel. Two representative compounds 1g and 2c can alleviate capsaicin-induced pain in the cheek model of mice through channel desensitization but not in TRPA1 knockout mice. Taken together, our findings demonstrate that photoswitchable TRPA1 agonists can be used as pharmacological tools for study of pain signaling.