Turning the Actin Nucleating Compound Miuraenamide into Nucleation Inhibitors.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
31 Aug 2021
31 Aug 2021
Historique:
received:
31
05
2021
accepted:
28
07
2021
entrez:
9
9
2021
pubmed:
10
9
2021
medline:
10
9
2021
Statut:
epublish
Résumé
Natural compounds that either increase or decrease polymerization of actin into filaments have become indispensable tools for cell biology. However, to date, it was not possible to use them as therapeutics due to their overall cytotoxicity and their unfavorable pharmacokinetics. Furthermore, their synthesis is in general quite complicated. In an attempt to find simplified analogues of miuraenamide, an actin nucleating compound, we identified derivatives with a paradoxical inversion of the mode of action: instead of increased nucleation, they caused an inhibition. Using an extensive computational approach, we propose a binding mode and a mode of action for one of these derivatives. Based on our findings, it becomes feasible to tune actin-binding compounds to one or the other direction and to generate new synthetic actin binders with increased functional selectivity.
Identifiants
pubmed: 34497907
doi: 10.1021/acsomega.1c02838
pmc: PMC8412923
doi:
Types de publication
Journal Article
Langues
eng
Pagination
22165-22172Informations de copyright
© 2021 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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