Design, synthesis, and mechanism of action of novel μ-conotoxin KIIIA analogues for inhibition of the voltage-gated sodium channel Nav1.7
Zitong Zhao, Teng Pan, Shen Chen, Peta J. Harvey, Jinghui Zhang, Xiao Li, Mengke Yang, Linhong Huang, Shoushi Wang, David J. Craik, Tao Jiang, Rilei Yu
Abstract
1.7 current. Intraperitoneally injected 37 exhibited potent in vivo analgesic activity in a formalin-induced inflammatory pain model, with activity reaching ∼350-fold of the positive control drug morphine. Overall, peptide 37 has a simplified disulfide-bond framework and exhibits potent in vivo analgesic effects and has promising potential for development as a pain therapy in the future.
Topics & Concepts
ChemistrySodium channelIn vivoConotoxinPeptideNAV1StereochemistrySodium channel blockerInhibitory postsynaptic potentialHEK 293 cellsPharmacologyBiochemistryReceptorSodiumBiologyNeuroscienceBiotechnologyOrganic chemistryNicotinic Acetylcholine Receptors StudyIon channel regulation and functionReceptor Mechanisms and Signaling