Exploratory Study on the RNA-Binding Structural Motifs by Library Screening Targeting pre-miRNA-29 a

Area of Science:

• Biochemistry and Molecular Biology
• Medicinal Chemistry
• Drug Discovery

Background:

• MicroRNA (miRNA) maturation is a critical metabolic pathway for modulating gene expression in various diseases.
• Targeting miRNA production offers a promising strategy for therapeutic intervention.

Purpose of the Study:

• To discover small molecules that bind to precursor miR-29a (pre-miR-29a).
• To identify structural motifs essential for pre-miR-29a binding.

Main Methods:

• Fluorescent indicator displacement (FID) assay screened a library of 41,119 compounds.
• Surface plasmon resonance (SPR) assay validated binding interactions with pre-miR-29a.
• Substructure analysis identified key binding motifs.

Main Results:

• FID assay identified 1075 potential binders.
• SPR assay confirmed 21 hit compounds with reproducible binding to pre-miR-29a.
• Five substructures were identified as potentially crucial for pre-miR-29a binding.

Conclusions:

• The combined FID and SPR screening approach is effective for discovering molecules that bind to target pre-miRNAs.
• This study provides novel chemical entities and structural insights for pre-miR-29a-targeted drug discovery.