Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Study on the Analgesic Activity of Peptide from Conus achates

Author(s): Xiujie Liu, Fuli Wang, Huilan Yu, Changcai Liu, Junmei Xia, Yangde Ma and Hui Jiang*

Volume 30, Issue 5, 2023

Published on: 08 May, 2023

Page: [367 - 373] Pages: 7

DOI: 10.2174/0929866530666230403095018

Price: $65

Abstract

Background: As a peptide originally discovered from Conus achates by mass spectrometry and cDNA sequencing, Ac6.4 contains 25 amino acid residues and three disulfide bridges. Our previous study found that this peptide possesses 80% similarity to MVIIA by BLAST and that MVIIA is a potent and selective blocker of N-type voltage-sensitive calcium channels in neurons.

Objective: To recognize the target protein and analgesic activity of Ac6.4 from Conus achates.

Methods: In the present study, we synthesized Ac6.4, expressed the Trx-Ac6.4 fusion protein, tested Ac6.4 for its inhibitory activity against Cav2.2 in CHO cells and investigated Ac6.4 and Trx-Ac6.4 for their analgesic activities in mice.

Results: Data revealed that Ac6.4 had strong inhibitory activity against Cav2.2 (IC50 = 43.6 nM). After intracranial administration of Ac6.4 (5, 10, 20 μg/kg) and Trx-Ac6.4 (20, 40, 80 μg/kg), significant analgesia was observed. The analgesic effects (elevated pain thresholds) were dose-dependent.

Conclusion: This study expands our knowledge of the peptide Ac6.4 and provides new possibilities for developing Cav2.2 inhibitors and analgesic drugs.

Keywords: N-type calcium ion channel, peptide, analgesic, Conus achates, Cav2.2, Ac6.4.

« Previous Next »
Graphical Abstract

[1]
Czerwiec, E.; Kalume, D.E.; Roepstorff, P.; Hambe, B.; Furie, B.; Furie, B.C.; Stenflo, J.; Clinical, C.M.; Klinisk, K.M.; Lund, U.; Lunds, U. Novel γ-carboxyglutamic acid-containing peptides from the venom of Conus textile. FEBS J., 2006, 273(12), 2779-2788.
[http://dx.doi.org/10.1111/j.1742-4658.2006.05294.x] [PMID: 16817904]
[2]
Favreau, P.; Gilles, N.; Lamthanh, H.; Bournaud, R.; Shimahara, T.; Bouet, F.; Laboute, P.; Letourneux, Y.; Ménez, A.; Molgó, J.; Le Gall, F. A new omega-conotoxin that targets N-type voltage-sensitive calcium channels with unusual specificity. Biochemistry, 2001, 40(48), 14567-14575.
[http://dx.doi.org/10.1021/bi002871r] [PMID: 11724570]
[3]
Gowd, K.H.; Dewan, K.K.; Iengar, P.; Krishnan, K.S.; Balaram, P. Probing peptide libraries from Conus achatinus using mass spectrometry and cDNA sequencing: Identification of δ and ω-conotoxins. J. Mass Spectrom., 2008, 43(6), 791-805.
[http://dx.doi.org/10.1002/jms.1377] [PMID: 18286662]
[4]
Liu, L.; Wu, X.; Yuan, D.; Chi, C.; Wang, C. Identification of a novel S-superfamily conotoxin from vermivorous Conus caracteristicus. Toxicon, 2008, 51(8), 1331-1337.
[http://dx.doi.org/10.1016/j.toxicon.2008.03.001] [PMID: 18423793]
[5]
Mould, J.; Yasuda, T.; Schroeder, C.I.; Beedle, A.M.; Doering, C.J.; Zamponi, G.W.; Adams, D.J.; Lewis, R.J. The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels. J. Biol. Chem., 2004, 279(33), 34705-34714.
[http://dx.doi.org/10.1074/jbc.M310848200] [PMID: 15166237]
[6]
Peigneur, S.; Tytgat, J. 14. When cone snails and spiders meet: Design of selective and potent sodium channel inhibitors. Toxicon, 2014, 91, 170.
[http://dx.doi.org/10.1016/j.toxicon.2014.08.022]
[7]
Schroeder, C.I.; Nielsen, K.J.; Adams, D.A.; Loughnan, M.; Thomas, L.; Alewood, P.F.; Lewis, R.J.; Craik, D.J. Effects of Lys2 to Ala2 substitutions on the structure and potency of ω-conotoxins MVIIA and CVID. Biopolymers, 2012, 98(4), 345-356.
[http://dx.doi.org/10.1002/bip.22031] [PMID: 23193599]
[8]
Zhu, X.; Bi, J.; Yu, J.; Li, X.; Zhang, Y.; Zhangsun, D.; Luo, S. Recombinant expression and characterization of α-conotoxin LvIA in Escherichia coli. Mar. Drugs, 2016, 14(1), 11.
[http://dx.doi.org/10.3390/md14010011] [PMID: 26742048]
[9]
Figueroa-Montiel, A.; Bernáldez, J.; Jiménez, S.; Ueberhide, B.; González, L.; Licea-Navarro, A. Antimycobacterial activity: A new pharmacological target for conotoxins found in the first reported conotoxin from Conasprella ximenes. Toxins (Basel), 2018, 10(2), 51.
[http://dx.doi.org/10.3390/toxins10020051] [PMID: 29360782]
[10]
Hendricks, J.R. Glowing seashells: Diversity of fossilized coloration patterns on coral reef-associated cone snail (Gastropoda: Conidae) shells from the Neogene of the Dominican Republic. PLoS One, 2015, 10(4), e0120924.
[http://dx.doi.org/10.1371/journal.pone.0120924] [PMID: 25830769]
[11]
Joachim, M.; Maguire, N.; Schäfer, J.; Gerlach, D.; Czermak, P. Process intensification for an insect antimicrobial peptide elastin-like polypeptide fusion produced in redox-engineered Escherichia coli. Front. Bioeng. Biotechnol., 2019, 7, 150.
[http://dx.doi.org/10.3389/fbioe.2019.00150] [PMID: 31316976]
[12]
Kelley, W.P.; Schulz, J.R.; Jakubowski, J.A.; Gilly, W.F.; Sweedler, J.V. Two toxins from Conus striatus that individually induce tetanic paralysis. Biochemistry, 2006, 45(47), 14212-14222.
[http://dx.doi.org/10.1021/bi061485s] [PMID: 17115716]
[13]
Kim, J.I.; Takahashi, M.; Ohtake, A.; Wakamiya, A.; Sato, K. Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N-type calcium channel blockers. Biochem. Biophys. Res. Commun., 1995, 206(2), 449-454.
[http://dx.doi.org/10.1006/bbrc.1995.1063] [PMID: 7826361]
[14]
Liu, L.; Chew, G.; Hawrot, E.; Chi, C.; Wang, C. Two Potent α3/5 Conotoxins from Piscivorous Conus achatinus. Acta Biochim. Biophys. Sin., 2007, 39(6), 438-444.
[http://dx.doi.org/10.1111/j.1745-7270.2007.00301.x] [PMID: 17558449]
[15]
Luo, S.; Zhangsun, D.; Lin, Q.; Xie, L.; Wu, Y.; Zhu, X. Sequence diversity of O-superfamily conopetides from Conus marmoreus native to Hainan. Peptides, 2006, 27(12), 3058-3068.
[http://dx.doi.org/10.1016/j.peptides.2006.08.013] [PMID: 17011667]
[16]
Nair, A.S.; Poornachand, A.; Kodisharapu, P.K. Ziconotide: Indications, adverse effects, and limitations in managing refractory chronic pain. Indian J. Palliat. Care, 2018, 24(1), 118-119.
[PMID: 29440821]
[17]
Olivera, B.M.; Cruz, L.J.; De Santos, V.; LeCheminant, G.; Griffin, D.; Zeikus, R.; McIntosh, J.M.; Galyean, R.; Varga, J.; Gray, W.R.; Et, A. Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using. omega.-conotoxin from Conus magus venom. Biochemistry, 1987, 26(8), 2086-2090.
[http://dx.doi.org/10.1021/bi00382a004] [PMID: 2441741]
[18]
Puillandre, N.; Watkins, M.; Olivera, B.M. Evolution of Conus peptide genes: Duplication and positive selection in the A-superfamily. J. Mol. Evol., 2010, 70(2), 190-202.
[http://dx.doi.org/10.1007/s00239-010-9321-7] [PMID: 20143226]
[19]
Safavi-Hemami, H.; Hu, H.; Gorasia, D.G.; Bandyopadhyay, P.K.; Veith, P.D.; Young, N.D.; Reynolds, E.C.; Yandell, M.; Olivera, B.M.; Purcell, A.W. Combined proteomic and transcriptomic interrogation of the venom gland of Conus geographus uncovers novel components and functional compartmentalization. Mol. Cell. Proteomics, 2014, 13(4), 938-953.
[http://dx.doi.org/10.1074/mcp.M113.031351] [PMID: 24478445]
[20]
Zhan, J.; Chen, X.; Wang, C.; Qiu, J.; Ma, F.; Wang, K.; Zheng, S. A fusion protein of conotoxin MVIIA and thioredoxin expressed in Escherichia coli has significant analgesic activity. Biochem. Biophys. Res. Commun., 2003, 311(2), 495-500.
[http://dx.doi.org/10.1016/j.bbrc.2003.09.234] [PMID: 14592443]
[21]
Turner, R.J.; Freeman, S.E. Factors affecting the muscle depolarization due to Conus achatinus toxin. Toxicon, 1974, 12(1), 49-55.
[http://dx.doi.org/10.1016/0041-0101(74)90098-1] [PMID: 4818646]
[22]
Yu, J.; Zhu, X.; Yang, Y.; Luo, S.; Zhangsun, D. Expression in Escherichia coli of fusion protein comprising α-conotoxin TxIB and preservation of selectivity to nicotinic acetylcholine receptors in the purified product. Chem. Biol. Drug Des., 2018, 91(2), 349-358.
[http://dx.doi.org/10.1111/cbdd.13104] [PMID: 28891599]
[23]
Yuan, D.D.; Han, Y.H.; Wang, C.G.; Chi, C.W. From the identification of gene organization of α conotoxins to the cloning of novel toxins. Toxicon, 2007, 49(8), 1135-1149.
[http://dx.doi.org/10.1016/j.toxicon.2007.02.011] [PMID: 17400270]

Rights & Permissions Print Cite
Article Metrics
24
3
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy