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Yale researchers develop way to attack RNA with small-molecule drugs

Yale researchers develop way to attack RNA with small-molecule drugs

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Yale researchers have developed a way to target RNA with small-molecule drugs, creating a new method for tapping into a vast number of biological mechanisms critical to metabolism and gene expression.

“There is tremendous interest in targeting RNA with small molecules,” said Yale biochemist Anna Pyle, whose lab conducted the research. “Despite this potential, there has been limited progress on the development of small-molecule drugs that bind RNA, and a pervasive view that RNA is not a viable therapeutic target.”

Pyle and her colleagues focused on RNA targets within pathogenic yeasts, opportunistic fungal organisms that are especially problematic for patients with compromised immune systems, including patients with implanted devices, neonatal patients, and cancer patients.

Pyle’s team identified small molecules that would inhibit a particular group of large, self-splicing ribozymes found in bacteria, plants, and fungi — but not found in mammals. These RNA molecules have an elaborate structure that contains tiny, solvent-accessible pockets for a small molecule drug to bind with the larger molecule.

The researchers also chose this group of RNA molecules because of their crucial role in fungal metabolism.

“Our work establishes that RNA is ‘druggable,’ and that refractory pathogens such as pathogenic fungi and drug-resistant bacteria can be attacked by targeting their unique RNA repertoire,” Pyle said. “It demonstrates that the burgeoning landscape of functional RNA elements contains a wealth of potential targets that can be modulated by small molecules, opening a new frontier in molecular pharmacology.”

https://news.yale.edu/2018/10/15/attacking-rna-small-molecule-drugsource: Yale University

Posted in: Drug Discovery & Pharmaceuticals | Molecular & Structural Biology | Biochemistry

Tags: Bacteria, Cancer, Drugs, Gene, Gene Expression, Metabolism, Molecule, OCT, Pharmacology, Research, RNA, Splicing

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