Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3
Abstractα-Conotoxins (α-CTxs) are small peptides composed of 11 to 20 amino acid residues with two disulfide bridges. Most of them potently and selectively target nicotinic acetylcholine receptor (nAChR) subtypes, and a few were found to inhibit the GABAB receptor (GABABR)-coupled N-type calcium channels (Cav2.2). However, in all of α-CTxs targeting both receptors, the disulfide connectivity arrangement “C1-C3, C2-C4” is present. In this work, a novel α4/7-CTx named Lt1.3 (GCCSHPACSGNNPYFC-NH2) was cloned from the venom ducts of Conus litteratus (C. litteratus) in the South China Sea. Lt1.3 was then chemically synthesized and two isomers with disulfide bridges “C1-C3, C2-C4” and “C1-C4, C2-C3” were found and functionally characterized. Electrophysiological experiments showed that Lt1.3 containing the common disulfide bridges “C1-C3, C2-C4” potently and selectively inhibited α3β2 nAChRs and not GABABR-coupled Cav2.2. Surprisingly, but the isomer with the disulfide bridges “C1-C4, C2-C3” showed exactly the opposite inhibitory activity, inhibiting only GABABR-coupled Cav2.2 and not α3β2 nAChRs. These findings expand the knowledge of the targets and selectivity of α-CTxs and provide a new structural motif to inhibit the GABABR-coupled Cav2.2. View Full-Text
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Chen, J.; Liang, L.; Ning, H.; Cai, F.; Liu, Z.; Zhang, L.; Zhou, L.; Dai, Q. Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3. Mar. Drugs 2018, 16, 112.
Chen J, Liang L, Ning H, Cai F, Liu Z, Zhang L, Zhou L, Dai Q. Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3. Marine Drugs. 2018; 16(4):112.Chicago/Turabian Style
Chen, Jinqin; Liang, Li; Ning, Huying; Cai, Fengtao; Liu, Zhuguo; Zhang, Longxiao; Zhou, Liangyi; Dai, Qiuyun. 2018. "Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3." Mar. Drugs 16, no. 4: 112.
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