Bis-3-Chloropiperidines Targeting TAR RNA as A Novel Strategy to Impair the HIV-1 Nucleocapsid Protein.
Molecules
; 26(7)2021 Mar 26.
Article
in En
| MEDLINE
| ID: mdl-33810333
ABSTRACT
Specific RNA sequences regulate functions essential to life. The Trans-Activation Response element (TAR) is an RNA stem-bulge-loop structure involved in several steps of HIV-1 replication. In this work, we show how RNA targeting can inhibit HIV-1 nucleocapsid (NC), a highly conserved protein known to catalyze nucleic acid melting and strand transfers during reverse transcription. Our RNA targeting strategy consists of the employment of bis-3-chloropiperidines (B-CePs) to impair RNA melting through bifunctional alkylation. Specific interactions between B-CePs and TAR RNA were analytically investigated by gel electrophoresis and mass spectrometry, allowing the elucidation of B-CePs' recognition of TAR, and highlighting an RNA-directed mechanism of protein inhibition. We propose that B-CePs can freeze TAR tridimensional conformation, impairing NC-induced dynamics and finally inhibiting its functions in vitro.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Piperidines
/
RNA, Viral
/
Gene Expression
/
HIV Long Terminal Repeat
/
HIV-1
/
Nucleocapsid Proteins
Language:
En
Year:
2021
Type:
Article