Back to Search Start Over

Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel α-Conotoxin with an Extended N-Terminal Tail

Authors :
Julien Giribaldi
Yves Haufe
Edward R. J. Evans
David T. Wilson
Norelle L. Daly
Christine Enjalbal
Annette Nicke
Sébastien Dutertre
Source :
Marine Drugs, Vol 19, Iss 3, p 141 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Cone snails are venomous marine predators that rely on fast-acting venom to subdue their prey and defend against aggressors. The conotoxins produced in the venom gland are small disulfide-rich peptides with high affinity and selectivity for their pharmacological targets. A dominant group comprises α-conotoxins, targeting nicotinic acetylcholine receptors. Here, we report on the synthesis, structure determination and biological activity of a novel α-conotoxin, CIC, found in the predatory venom of the piscivorous species Conus catus and its truncated mutant Δ-CIC. CIC is a 4/7 α-conotoxin with an unusual extended N-terminal tail. High-resolution NMR spectroscopy shows a major influence of the N-terminal tail on the apparent rigidity of the three-dimensional structure of CIC compared to the more flexible Δ-CIC. Surprisingly, this effect on the structure does not alter the biological activity, since both peptides selectively inhibit α3β2 and α6/α3β2β3 nAChRs with almost identical sub- to low micromolar inhibition constants. Our results suggest that the N-terminal part of α-conotoxins can accommodate chemical modifications without affecting their pharmacology.

Details

Language :
English
ISSN :
16603397
Volume :
19
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Marine Drugs
Publication Type :
Academic Journal
Accession number :
edsdoj.2dc252aa21af48058c665c294209a762
Document Type :
article
Full Text :
https://doi.org/10.3390/md19030141