Study on the Analgesic Activity of Peptide from Conus achates

• Published in: Protein and peptide letters Vol. 30; no. 5; p. 367
• Main Authors: Liu, Xiujie, Wang, Fuli, Yu, Huilan, Liu, Changcai, Xia, Junmei, Ma, Yangde, Jiang, Hui
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2023
• Subjects: Analgesics - chemistry; Analgesics - pharmacology; Animals; Calcium Channels, N-Type - metabolism; Conus Snail - chemistry; Conus Snail - metabolism; Cricetinae; Cricetulus; Mice; Peptides - chemistry; Conus achates; peptide; Ac6.4; N-type calcium ion channel; analgesic; Cav2.2
• ISSN: 1875-5305
• DOI: 10.2174/0929866530666230403095018

As a peptide originally discovered from 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. To recognize the target protein and analgesic activity of Ac6.4 from . 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. Data revealed that Ac6.4 had strong inhibitory activity against Cav2.2 (IC = 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. This study expands our knowledge of the peptide Ac6.4 and provides new possibilities for developing Cav2.2 inhibitors and analgesic drugs.