靶向TRPV1受体的蜈蚣毒素环肽cRhTx的合成及活性研究

摘 要：目的 合成首尾环化的蜈蚣毒素环肽（cRhTx），评价它对TRPV1配体门控离子通道的影响。方法 采用Fmoc-固液相联用多肽合成技术和反相高效液相色谱-质谱联用技术制备野生型蜈蚣毒素（RhTx）与cRhTx，利用圆二色谱法分析两者的结构特点，并进一步采用电生理学法检测两者对TRPV1受体激活的影响。结果 首次通过引入GGAAGG柔性连接片段合成了结构新颖的cRhTx，cRhTx和RhTx具有较高的结构相似性，且cRhTx对TRPV1受体的激动作用与RhTx相似。结论 引入GGAAGG柔性连接片段，对野生型RhTx进行环化，可以保持对TRPV1的激动作用，获得的cRhTx具有重要应用潜力。

Synthesis and Biological Activity Study of Cyclized Centipede Toxin cRhTx against TRPV1

Abstract: Objective N, C-termini cyclized centipede toxin RhTx (cRhTx) was synthesized, and the structural difference between the cRhTx and the wild-type RhTx was compared, and the activating difference of the TRPV1 ligand-gated ion channel was analyzed. Methods cRhTx and wild-type RhTx were synthesized by Fmoc-SPPS and LC-MS. Structures of cRhTx and wild-type RhTx were analyzed by circular dichroism. Electrophysiological methods were used to compare the activation of TRPV1 between cRhTx and wild-type RhTx. Results cRhTx was successfully synthesized firstly through grafting linker (GGAAGG). CD spectra showed structural similarity between cRhTx and wild-type RhTx. The cRhTx had a slightly stronger agonistic effect on TRPV1 than RhTx. Conclusion Introduction of GGAAGG flexible ligation fragment, cyclization of wild-type RhTx, can maintain the agonistic effect on TRPV1, and the finally obtained cRhTx has great application potential.