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Related Experiment Video

Updated: Sep 9, 2025

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

Streamlined Fragment-Based Discovery Platform for Targeting Structured RNAs.

Yilin Jia^1,2, Amirhossein Taghavi¹, Patrick R A Zanon¹

¹Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, Florida 33458, United States.

ACS Chemical Biology

|August 29, 2025

Summary

This summary is machine-generated.

This study introduces a new platform for fragment-based drug discovery targeting RNA. It uses novel chemical tags to visualize and optimize small molecules for treating diseases like myotonic dystrophy type 1.

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Last Updated: Sep 9, 2025

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Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions

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Published on: September 28, 2017

Area of Science:

Biochemistry
Chemical Biology
Drug Discovery

Background:

Fragment-based drug discovery (FBDD) traditionally uses spectrometric methods.
Identifying low-affinity binders to biomolecules is crucial for FBDD.
Targeting RNA with small molecules presents unique challenges.

Purpose of the Study:

To develop a streamlined fragment-based screening platform for small molecules targeting RNA.
To demonstrate proof-of-concept for this novel platform.
To identify fragments binding to specific RNA structures implicated in disease.

Main Methods:

Utilized low molecular weight fragments with diazirine and alkyne tags.
Employed photolysis followed by click chemistry with a fluorophore for visualization.
Screened fragments against the r(CUG) repeat expansion RNA associated with myotonic dystrophy type 1.

Main Results:

Identified fragments binding to 1x1 nucleotide U/U internal loops in the target RNA.
Designed homodimeric compounds that interact with adjacent internal loops.
Developed a dimeric compound with enhanced affinity, converted to a covalent binder for sustained target engagement.

Conclusions:

Established a versatile platform for targeting structured RNAs.
Demonstrated the potential for developing therapeutics against RNA targets.
The platform has broad applications for various disease-relevant RNA targets.