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Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3.
- Source :
- Marine Drugs; Apr2018, Vol. 16 Issue 4, p112, 1p
- Publication Year :
- 2018
-
Abstract
- α-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 GABA<subscript>B</subscript> receptor (GABA<subscript>B</subscript>R)-coupled N-type calcium channels (Cav2.2). However, in all of α-CTxs targeting both receptors, the disulfide connectivity arrangement “C<superscript>1</superscript>-C<superscript>3</superscript>, C<superscript>2</superscript>-C<superscript>4</superscript>” is present. In this work, a novel α4/7-CTx named Lt1.3 (GCCSHPACSGNNPYFC-NH<subscript>2</subscript>) was cloned from the venom ducts of <italic>Conus litteratus</italic> (<italic>C. litteratus</italic>) in the South China Sea. Lt1.3 was then chemically synthesized and two isomers with disulfide bridges “C<superscript>1</superscript>-C<superscript>3</superscript>, C<superscript>2</superscript>-C<superscript>4</superscript>” and “C<superscript>1</superscript>-C<superscript>4</superscript>, C<superscript>2</superscript>-C<superscript>3</superscript>” were found and functionally characterized. Electrophysiological experiments showed that Lt1.3 containing the common disulfide bridges “C<superscript>1</superscript>-C<superscript>3</superscript>, C<superscript>2</superscript>-C<superscript>4</superscript>” potently and selectively inhibited α3β2 nAChRs and not GABA<subscript>B</subscript>R-coupled Cav2.2. Surprisingly, but the isomer with the disulfide bridges “C<superscript>1</superscript>-C<superscript>4</superscript>, C<superscript>2</superscript>-C<superscript>3</superscript>” showed exactly the opposite inhibitory activity, inhibiting only GABA<subscript>B</subscript>R-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 GABA<subscript>B</subscript>R-coupled Cav2.2. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16603397
- Volume :
- 16
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Marine Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 129521593
- Full Text :
- https://doi.org/10.3390/md16040112