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Harnessing the Power of Nitrogen: Oklahoma University’s Game-Changing Drug Development Breakthrough
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Researchers at the University of Oklahoma have developed an innovative method to add a single nitrogen atom to a molecule, opening up new avenues in drug research and development. Published in the renowned journal Science, this groundbreaking study has already caught the attention of international pharmaceutical producers.
Nitrogen atoms and nitrogen-containing chemical structures, known as heterocycles, play a crucial role in drug chemistry and drug development. Led by Associate Professor Indrajeet Sharma, a team at OU has demonstrated that using short-lived chemicals called sulfenylnitrenes, they can insert nitrogen atoms into bioactive molecules, transforming them into novel pharmacophores for drug creation.
This innovative process, known as framework editing, is inspired by Sir Derek Barton, winner of the 1969 Nobel Prize in Chemistry. Sharma highlights the significance of nitrogen in drug development, stating, "About 85% of FDA-approved drugs have one or more nitrogen atoms, and if you look at the top 200 bestselling drugs, 75-80% contain nitrogen heterocycles."
By selectively adding nitrogen atoms to existing drug hetercycles late in the development process, Sharma’s team can alter a molecule’s biological and pharmacological properties without changing its function. This approach could explore untapped chemical space for drug discovery.
Sharma envisions this framework editing process enabling a wider range of drugs, as scientists can forge new-drug series by adding a single nitrogen atom instead of developing new drugs from scratch. Nitrogen’s essential role in DNA, RNA, proteins, and amino acids makes Sharma’s research promising for treating conditions like cancer and neurological disorders.
Previous research in this field has proposed similar concepts but relied on conventional nitrenes and produced excessive oxidizing agents, incompatible with many drug molecules. Sharma’s team employs a method to generate sulfenylnitrenes that are adjuvant-free, metal-free, and compatible with other functional groups in molecules.
"Many drug prices depend on the number of steps involved in their production," Sharma notes. "Pharmaceutical companies are interested in finding ways to reduce these steps. By adding nitrogen atoms later in the development process, we can create new drugs more cheaply, like renovating a building, not starting from scratch."
Sharma’s work also has implications for healthcare accessibility. "Even in the U.S., healthcare spending per capita reaches over $12,000 annually. If we can simplify the large-scale production of drugs, we can lower treatment costs for vulnerable populations worldwide."
More Information:
Bidhan Ghosh et al, Nitrogen atom insertion mediated by Sulfenylnitrene for late-stage N-heterocycle framework editing, Science (2025). DOI: 10.1126/science.adp0974
