Synthesis, Structural and Pharmacological Characterizations of CIC, a Novel α-Conotoxin with an Extended N-Terminal Tail.
Mar Drugs
; 19(3)2021 Mar 02.
Article
in En
| MEDLINE
| ID: mdl-33801301
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 α3ß2 and α6/α3ß2ß3 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nicotinic Antagonists
/
Conotoxins
/
Conus Snail
/
Mollusk Venoms
Limits:
Animals
Language:
En
Journal:
Mar Drugs
Journal subject:
BIOLOGIA
/
FARMACOLOGIA
Year:
2021
Document type:
Article
Affiliation country: