Study on the Analgesic Activity of Peptide from Conus achates.

IF 1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Protein and Peptide Letters Pub Date : 2023-01-01 DOI:10.2174/0929866530666230403095018

Xiujie Liu, Fuli Wang, Huilan Yu, Changcai Liu, Junmei Xia, Yangde Ma, Hui Jiang

{"title":"Study on the Analgesic Activity of Peptide from Conus achates.","authors":"Xiujie Liu, Fuli Wang, Huilan Yu, Changcai Liu, Junmei Xia, Yangde Ma, Hui Jiang","doi":"10.2174/0929866530666230403095018","DOIUrl":null,"url":null,"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.","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein and Peptide Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0929866530666230403095018","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

松果附着物肽镇痛活性的研究。

背景:Ac6.4由25个氨基酸残基和3个二硫桥组成，是一种通过质谱分析和cDNA测序从Conus achates中发现的肽。我们之前的研究发现，该肽与BLAST发现的MVIIA具有80%的相似性，并且MVIIA是神经元中n型电压敏感钙通道的有效和选择性阻断剂。目的:鉴定松果Ac6.4的靶蛋白及其镇痛活性。方法:本研究合成Ac6.4，表达Trx-Ac6.4融合蛋白，在CHO细胞中检测Ac6.4对Cav2.2的抑制活性，并研究Ac6.4和Trx-Ac6.4对小鼠的镇痛作用。结果:Ac6.4对Cav2.2具有较强的抑制活性(IC50 = 43.6 nM)。经颅内给药Ac6.4(5、10、20 μg/kg)和Trx-Ac6.4(20、40、80 μg/kg)后，镇痛效果显著。镇痛效果(疼痛阈值升高)呈剂量依赖性。结论:本研究扩大了我们对肽Ac6.4的认识，为开发Cav2.2抑制剂和镇痛药物提供了新的可能性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis