Expanding the known structure space for RNA binding: a test of 2,5-diketopiperazine.
Org Biomol Chem
; 20(3): 606-612, 2022 01 19.
Article
em En
| MEDLINE
| ID: mdl-34927652
ABSTRACT
As the importance of RNA as a therapeutic target has become increasingly recognized, the need for new chemotypes able to bind RNA has grown in significance. We hypothesized that diketopiperazines (DKPs), common substructures in natural products and protein-targeting therapeutic agents, could serve as effective scaffolds for targeting RNA. To confirm this hypothesis, we designed and synthesized two analogs, one incorporating a DKP and one not, of compounds previously demonstrated to bind an RNA critical to the life cycle of HIV-1 with high affinity and specificity. Prior to compound synthesis, calculations employing density functional methods and molecular mechanics conformational searches were used to confirm that the DKP could present functionality in a similar (albeit not identical) orientation to the non DKP-containing compound. We found that both the DKP-containing and parent compound had similar affinities to the target RNA as measured by surface plasmon resonance (SPR). Both compounds were found to have modest but equal anti-HIV activity. These results establish the feasibility of using DKPs to target RNA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Produtos Biológicos
/
RNA Viral
/
HIV
/
Fármacos Anti-HIV
/
Dicetopiperazinas
Idioma:
En
Revista:
Org Biomol Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos