Fluorescent‐ and tagged‐protoxin II peptides: potent markers of the Na_v1.7 channel pain target

Background and Purpose Protoxin II (ProTx II) is a high affinity gating modifier that thought to selectively block the Na v 1.7 voltage‐dependent + channel, major therapeutic target for control of pain. We aimed at producing ProTx analogues entitled with novel functionalities cell distribution studies biochemical characterization its channel targets. Experimental Approach took advantage properties peptide, combined slow off rate, design number new tagged useful imaging biochemistry purposes. used high‐throughput automated patch‐clamp identify best matching native validated them on various ‐expressing cells in pull‐down studies. Key Results Two produced analogues, Biot‐ProTx ATTO488‐ProTx II, emulate pharmacological unlabelled whereas other remain blockers 1.7. The biotinylated version efficiently works several isoforms tested concentration‐dependent manner, fluorescent specifically labels over experimental conditions. Conclusions Implications these as tools purification pave way better understanding receptors pain their pathophysiological implications sensory neuronal processing. should also be drug screening strategies.