1562-93-2Relevant articles and documents
Photosensitive and Photoswitchable TRPA1 Agonists Optically Control Pain through Channel Desensitization
Luo, Jiajie,Qi, Hang,Qiao, Zhen,Tang, Xiaowen,Tang, Yi-Quan,Wang, KeWei,Wei, Ningning,Yin, Zhengji,Zhang, Yanru,Zhou, Qiqi,Zhu, Wei
supporting information, p. 16282 - 16292 (2021/11/12)
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.
A Time-Resolved Single-Molecular Train Based on Aerolysin Nanopore
Ying, Yi-Lun,Li, Zi-Yuan,Hu, Zheng-Li,Zhang, Junji,Meng, Fu-Na,Cao, Chan,Long, Yi-Tao,Tian, He
supporting information, p. 1893 - 1901 (2018/06/20)
An aerolysin nanopore interface was introduced as a molecular machine to electrically read out the real-time photo-controlled motion of an azobenzene-geared DNA train with high spatial and temporal resolution. Under alternating UV and visible irradiation, each DNA train performed two regulated speeds of 1.9 and 6.3 bases/s corresponding to trans and cis states, respectively, with readily identified current signals. Each train type fell into the ultra-narrow current population with a full-width half maximum of 0.2–0.4 pA. The combination of a model molecular machine system and powerful aerolysin interface enabled the motions of every artificial molecular machine to be followed in real time. The molecular motion study of a single-molecule machine is essential for excluding the average effect and investigating the mechanistic features of an individual machine at its precise state. To achieve this goal, we developed a small molecular “train” on a nanopore single-molecule interface for the real-time study of the light-regulated motion of a single train. Under alternate UV-visible irradiation, different motions were successfully discriminated at the single-molecule level with ultra-high resolution. Moreover, direct correlation of the motion of molecular machines to time-series readouts and real-time tracing was achieved. A light-switchable single-molecule train was developed on a nanopore single-molecule interface. Upon light regulation, a real-time motion study of a single-molecular machine was achieved. The translocation behavior of trans- and cis-Azo DNA trains through the nanopore platform showed distinctive differences both in speed and in current signal, which could be well discriminated at ultra-high resolution.
Structural stability of the photo-responsive DNA duplexes containing one azobenzene: Via a confined pore
Meng, Fu-Na,Li, Zi-Yuan,Ying, Yi-Lun,Liu, Shao-Chuang,Zhang, Junji,Long, Yi-Tao
supporting information, p. 9462 - 9465 (2017/09/01)
Herein, the structural stability of single azobenzene modified DNA duplexes, including the trans form and cis form, has been examined separately based on their distinguishable unzipping kinetics from the mixture by an α-hemolysin nanopore. Furthermore, the accurate isomerization efficiency between the trans and cis form was obtained with single molecule resolution.
