Expanding the known structure space for RNA binding: a test of 2,5-diketopiperazine.

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) orie

SUBMITTER: Arevalo DM 

PROVIDER: S-EPMC8900054 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature