Design And Synthesize The Ligands Of Transient Receptor Potential Channels

The two members of the TRP channels family TRPV1and TRPM2activated bythe capsaicin and ADPR respectively mediated the calcium ions influx introduce pain,diabetes, neurodegenerative diseases and so on. Consequently, the research on the twochannels’ gating mechanism became a new hot spot. According to previous researchand literature summary, a series of capsaicin analogues which can activate the TRPV1were designed and synthesized, and ADPR which can activate the TRPM2decoratedby the fluorescent group was researched preliminary in this paper.Through detailed study on the capsaicin structure4-(aminomethyl)-2-methoxy-phenol was chosen as the skeleton, and different length and structure of carboxylicacids have been introduced to the amino of the4-(aminomethyl)-2-methoxyphenol.Thus, a series of capsaicin analogues and capsaicin fluorescent sensors have beendesigned and synthesized as TRPV1’s activating agent and the structures confirmedby1H NMR.All the synthesized compounds were tested in vitro for activating the TRPV1channel，and the results revealed these conclusions:1.The more number of the capsaicin analogues’ tail carbon atom is,the strongerability of activating the TRPV1is. The compound whose tail has less5carbon atoms, has weak activation.While the compound whose tail has more5carbon atoms, has stronger activation. And when the tail reaches11carbonatoms, the activation of compound is close to the activation of capsaicin.2.The compounds that have phenyl group on the end of the tail have the ability ofactivating the TRPV1channel.3.Capsaicin fluorescent sensor has prominent fluorescence intensity and theability of activating the TRPV1channels.Through detailed study on the ADPR structure,we designed a ADPR fluorescentsensor and researched the compound of synthesis preliminarily.