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Ribbon Α-Conotoxin Ktm Exhibits Potent Inhibition Of Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Lisa R. Warner, Matthew D. King, James R. Groome, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3β2-nicotinic acetylcholine receptors (rα3β2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3β2-nAChRs by KTM (IC₅₀ = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC₅₀ = …