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Background: Conotoxins exhibit great potential as neuropharmacology tools and therapeutic candidates due to their high affinity and specificity for ion channels, neurotransmitter receptors or transporters. The traditional methods to discover new conotoxins are peptide purification from the crude venom or gene amplification from the venom duct., Methods: In this study, a novel O1 superfamily conotoxin Tx6.7 was directly cloned from the genomic DNA of Conus textile using primers corresponding to the conserved intronic sequence and 3' UTR elements. The mature peptide of Tx6.7 (DCHERWDWCPASLLGVIYCCEGLICFIAFCI) was synthesized by solid-phase chemical synthesis and confirmed by mass spectrometry., Results: Patch clamp experiments on rat DRG neurons showed that Tx6.7 inhibited peak calcium currents by 59.29 ± 2.34% and peak potassium currents by 22.33 ± 7.81%. In addition, patch clamp on the ion channel subtypes showed that 10 μM Tx6.7 inhibited 56.61 ± 3.20% of the hCa V 1.2 currents, 24.67 ± 0.91% of the hCa V 2.2 currents and 7.30 ± 3.38% of the hNa V 1.8 currents. Tx6.7 had no significant toxicity to ND7/23 cells and increased the pain threshold from 0.5 to 4 hours in the mouse hot plate assay., Conclusion: Our results suggested that direct cloning of conotoxin sequences from the genomic DNA of cone snails would be an alternative approach to obtaining novel conotoxins. Tx6.7 could be used as a probe tool for ion channel research or a therapeutic candidate for novel drug development., Competing Interests: Competing interests : The authors declare that they have no competing interests.

A substrate-controlled stereoselective semi-reduction of alkynes with MeOH as the hydrogen source has been developed, and readily available Cu(OAc) 2 (copper acetate) is utilized as an optimal catalyst. The detailed investigation of the mechanism revealed distinct catalytic processes for the ( Z )- and ( E )-alkenes, respectively. As a result, a diversity of alkynes (including terminal, internal alkynes etc.) were compatible under the mild reaction conditions. Furthermore, the high proportion of deuterium in Z -alkenes (up to 96%) was obtained using d 4 -methanol as a solvent., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)