Effects of Cyclization on Activity and Stability of α-Conotoxin TxIB.
activity
cyclization
stability
α-conotoxin TxIB
α6/α3β2β3 nAChRs
Journal
Marine drugs
ISSN: 1660-3397
Titre abrégé: Mar Drugs
Pays: Switzerland
ID NLM: 101213729
Informations de publication
Date de publication:
29 Mar 2020
29 Mar 2020
Historique:
received:
21
02
2020
revised:
25
03
2020
accepted:
25
03
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
22
12
2020
Statut:
epublish
Résumé
α-Conotoxin TxIB specifically blocked α6/α3β2β3 acetylcholine receptors (nAChRs), and it could be a potential probe for studying addiction and other diseases related to α6/α3β2β3 nAChRs. However, as a peptide, TxIB may suffer from low stability, short half-life, and poor bioavailability. In this study, cyclization of TxIB was used to improve its stability. Four cyclic mutants of TxIB (cTxIB) were synthesized, and the inhibition of these analogues on α6/α3β2β3 nAChRs as well as their stability in human serum were measured. All cyclized analogues had similar activity compared to wild-type TxIB, which indicated that backbone cyclization of TxIB had no significant effect on its activity. Cyclization of TxIB with a seven-residue linker improved its stability significantly in human serum. Besides this, the results showed that cyclization maintained the activity of α-conotoxin TxIB, which is conducive to its future application.
Identifiants
pubmed: 32235388
pii: md18040180
doi: 10.3390/md18040180
pmc: PMC7230940
pii:
doi:
Substances chimiques
Conotoxins
0
Conus textile toxin
0
Nicotinic Antagonists
0
Receptors, Nicotinic
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 81660585
Organisme : National Natural Science Foundation of China
ID : 81872794
Organisme : the 111 Project
ID : D20010
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