In Silico Discovery of Group II Intron RNA Splicing Inhibitors.
ACS Chem Biol
; 18(9): 1968-1975, 2023 09 15.
Article
in En
| MEDLINE
| ID: mdl-37602469
ABSTRACT
Here, we describe the discovery of compounds that inhibit self-splicing in group II introns. Using docking calculations, we targeted the catalytic active site within the Oceanobacillus iheyensis group IIC intron and virtually screened a library of lead-like compounds. From this initial virtual screen, we identified three unique scaffolds that inhibit splicing in vitro. Additional tests revealed that an analog of the lead scaffold inhibits splicing in an intron-dependent manner. Furthermore, this analog exhibited activity against the group II intron from a different class the yeast ai5γ IIB intron. The splicing inhibitors we identified could serve as chemical tools for developing group II intron-targeted antifungals, and, more broadly, our results highlight the potential of in silico techniques for identifying bioactive hits against structured and functionally complex RNAs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA
/
Antifungal Agents
Language:
En
Journal:
ACS Chem Biol
Year:
2023
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA