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PEARL-seq: A Photoaffinity Platform for the Analysis of Small Molecule-RNA Interactions
Herschel Mukherjee1, J Craig Blain1, Lee E Vandivier1
1Arrakis Therapeutics, 830 Winter Street, Waltham, Massachusetts, United States.
ACS Chemical Biology
|August 18, 2020
Summary
We developed Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq) to map small molecule binding sites on RNA. This method aids in the rational design of new RNA-targeting therapeutics.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- RNA is a crucial target for novel therapeutic development.
- Analyzing small molecule-RNA interactions is essential for rational drug design but lacks sufficient methods.
- Current methods for studying small molecule-RNA interactions are limited.
Purpose of the Study:
- To develop a platform for analyzing small molecule-RNA interactions.
- To enable rapid identification of small molecule binding sites on RNA targets.
- To provide insights into ligand selectivity across different RNA molecules.
Main Methods:
- Photoaffinity labeling technique.
- Photoaffinity Evaluation of RNA Ligation-Sequencing (PEARL-seq).
- Integration of small molecule structure-activity relationship (SAR) data and RNA probing data.
Main Results:
- PEARL-seq enables rapid identification of small molecule binding locations on RNA.
- The method provides information on ligand selectivity across various RNA targets.
- Generated data facilitates the construction of computational models for RNA-ligand structures.
Conclusions:
- PEARL-seq is a valuable platform for studying small molecule-RNA interactions.
- The developed method supports the rational design of novel RNA-targeted ligands.
- This approach advances the development of RNA-based therapeutics.
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