Structure-Activity Analysis of N-Type Calcium Channel Inhibitor SO-3

Minxing Dong, Fei Wang, Zhenzhen Yan, Shuo Yu, Juanjuan Wei, Qiaoling Wu, Zhuguo Liu, Yifei Tang, Jiuping Ding, Qiuyun Dai

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

As an ω-conopeptide originally discovered from Conus striatus, SO-3 contains 25 amino acid residues and three disulfide bridges. Our previous study has shown that this peptide possesses potent analgesic activity in rodent pain models (mouse and rat), and it specifically inhibits an N-type calcium ion channel (Cav2.2). In the study presented here, we investigated the key amino acid residues for their inhibitory activity against Cav2.2 expressed in HEK 293 cells and analgesic activity in mice. To improve the inhibitory activity of SO-3, we also evaluated the effects of some amino acid residues derived from the corresponding residues of ω-peptide MVIIA, CVID, or GVIA. Our data reveal that Lys6, Ile11, and Asn14 are the important functional amino acid residues for SO-3. The replacement of some amino acid residues of SO-3 in loop 1 with the corresponding residues of CVID and GVIA improved the inhibitory activity of SO-3. The binding mode of Cav2.2 with SO-3 amino acids in loop 1 and loop 2 may be somewhat different from that of MVIIA. This study expanded our knowledge of the structure-activity relationship of ω-peptides and provided a new strategy for improving the potency of Cav2.2 inhibitors.

Original languageEnglish
Pages (from-to)6349-6355
Number of pages7
JournalBiochemistry
Volume57
Issue number44
DOIs
Publication statusPublished - 6 Nov 2018
Externally publishedYes

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