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Synthesis and biological activity study of the retro-isomer of RhTx against TRPV1
TRPV1 is a ligand-gated ion channel and plays an important role in detecting noxious heat and pain with an unknown mechanism. RhTx from Chinese red-headed centipede activates the TRPV1 channel through the heat activation pathway by binding to the outer pore region, and causes extreme pain. Here, we...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9048425/ https://www.ncbi.nlm.nih.gov/pubmed/35494567 http://dx.doi.org/10.1039/c9ra08829f |
Sumario: | TRPV1 is a ligand-gated ion channel and plays an important role in detecting noxious heat and pain with an unknown mechanism. RhTx from Chinese red-headed centipede activates the TRPV1 channel through the heat activation pathway by binding to the outer pore region, and causes extreme pain. Here, we synthesized RhTx and its retro-isomer RL-RhTx. Their structures were investigated by their circular dichroic spectra and NMR spectra. The effect of RhTx and RL-RhTx on the currents of wild-type and mutants of TRPV1 indicated that RL-RhTx have comparable TRPV1 activation responses to RhTx. A mutagenesis study showed that four TRPV1 residues, including Leu461, Asp602, Tyr632 and Thr634, significantly contributed to the activation effects of RL-RhTx and RhTx, and both peptides probably bind with TRPV1 in similar binding modes. As a novel TRPV1 activator, RL-RhTx provides an essential powerful tool for the investigation of activation mechanisms of TRPV1. |
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