Chemical modifications of G418 (geneticin): Synthesis of novel readthrough aminoglycosides results in an improved in vitro safety window but no improvements in vivo.
Journal
Carbohydrate research
ISSN: 1873-426X
Titre abrégé: Carbohydr Res
Pays: Netherlands
ID NLM: 0043535
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
09
03
2020
revised:
17
05
2020
accepted:
01
06
2020
pubmed:
14
7
2020
medline:
1
6
2021
entrez:
14
7
2020
Statut:
ppublish
Résumé
G418 is currently the most potent and active aminoglycoside to promote readthrough of eukaryotic nonsense mutations. However, owing to its toxicity G418 cannot be used in vivo to study readthrough activity A robust and scalable method for selective derivatization of G418 was developed to study the biological activity and toxicity of a series of analogs. Despite our synthetic efforts, an improvement in readthrough potency was not achieved. We discovered several analogs that demonstrated reduced zebra fish hair cell toxicity (a surrogate for ototoxicity), but this reduction in cellular toxicity did not translate to reduced in vivo toxicity in rats.
Identifiants
pubmed: 32658832
pii: S0008-6215(20)30150-6
doi: 10.1016/j.carres.2020.108058
pii:
doi:
Substances chimiques
Aminoglycosides
0
Gentamicins
0
antibiotic G 418
A08F5XTI6G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108058Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.