Discovery of a Novel Cysteine Framework XXIV Conotoxin from Conus striatus , S24a, with Potential Analgesic Activity
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Discovery of a Novel Cysteine Framework XXIV Conotoxin from Conus striatus, S24a, with Potential Analgesic Activity Yuanyuan Qiang1 · Jianguo Niu1 · Yun Wu2 · Zhao Di3 · Feng Wang1 · Lianxiang Zhang1 · Kunmei Liu1 · Boyao Zhao4 · Lei Wang5 Accepted: 19 August 2020 © Springer Nature B.V. 2020
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. Keywords Conotoxin · S24a · A-superfamily · Fusion expression · Analgesic activity
Introduction Marine Conus belongs to the mollusk Phyllopoda Conus family, and there are approximately 700 species in the world, mainly distributed in the South China Sea, the Pacific Yuanyuan Qiang, Jianguo Niu, and Yun Wu have contributed equally to this work. * Lei Wang [email protected] 1
Ningxia Key Laboratory for Cerebrocranical Disease, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750001, Ningxia, China
2
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guang Dong Medical University, Dongguan 523808, China
3
Department of Respiratory Medcine, People’s Hospital of Ningxia Hui Autonomous Region, 301 ZHengyuan north road, Yinchuan 750001, Ningxia, China
4
Department of Maxillofacial Surgery, Yinchuan Stomatology Hospital, 157 Zheng yuan road, Yinchuan 750001, Ningxia, China
5
Department of Pharmaceutical Engineering, College of Materials and Energy, South China Agricultural University, Guangzhou 510642, China
Ocean, Australia and other places. Conus can secrete cocktails of mixed neurotoxins, known as conotoxins. It has been reported that each conus contains approximately 100–200 different sequence structures of conotoxins (Olivera 1997). There are 2000 conotoxin nucleic acid sequences, and 8000 conotoxin protein sequences have been reported. Conotoxins are small disulfide-bonded peptides that act as remarkable selective inhibitors and modulators of ion channels (sodium, potassium, calcium), noradrenaline transporters, neurotensin receptors, nicotinic acetylcholine receptors and N-methyl-d-aspartate receptors (Mir et al. 2016; Olivera 2006). Conotoxins have a short sequence, abundant cysteine skeleton structure and various posttranslatio
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