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Discovery of a Novel Cysteine Framework XXIV Conotoxin from Conus striatus, S24a, with Potential Analgesic Activity

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Abstract

A novel conotoxin, S24a, containing 26 amino acid residues was first derived from the cDNA library of Conus striatus. This conotoxin has the same conserved signal peptide as A-superfamily conotoxins and some unconserved residues in the pro-region. According to the mature peptide sequence of this conotoxin, S24a was prepared by the Escherichia coli expression system and purified by affinity chromatography, Sephadex gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC). The molecular weight of S24a was identified by MALDI-TOF-MS. Biological function experiments showed that S24a could inhibit frog sciatic nerve muscle contraction. Moreover, a high dose of S24a (100 μg/kg) had more potent and longer lasting analgesic activity compared with lidocaine and pethidine in the hotplate pain model and the formalin pain model in mice, which indicated that S24a can be further developed as a potential analgesic drug lead.

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Funding

This work was supported by grants from the Key Research and Development Project of Ningxia Hui Autonomous Region (Grant No. 2019BEB04015).

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QYY carried out most of the experimental work and was responsible for drafting the manuscript; WY performed the animal experiments; NJG conducted the analysis of data; WL provided scientific and administrative oversight for the conduct of the research and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Lei Wang.

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We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work.

Ethics Approval

These specimens in this research were collected from the sea near Sanya in China, and we declare that the purposes of the collected samples are only for scientific research, not for other commercial purposes, and do not involve endangered or protected species. All animal procedures were carried out according to the approved protocol of the Institutional Animal Care and Use Committee at the Sun Yat-sen University.

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Qiang, Y., Niu, J., Wu, Y. et al. Discovery of a Novel Cysteine Framework XXIV Conotoxin from Conus striatus, S24a, with Potential Analgesic Activity. Int J Pept Res Ther 27, 615–625 (2021). https://doi.org/10.1007/s10989-020-10109-4

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