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KAIST Changes the Paradigm of Drug Discovery with World's First Atomic Editing In pioneering drug development, the new technology that enables the easy and rapid editing of key atoms responsible for drug efficacy has been regarded as a fundamental and "dream" technology, revolutionizing the process of discovering potential drug candidates. KAIST researchers have become the first in the world to successfully develop single-atom editing technology that maximizes drug efficacy. On October 8th, KAIST (represented by President Kwang-Hyung Lee) announced that Professor Yoonsu Park’s research team from the Department of Chemistry successfully developed technology that enables the easy editing and correction of oxygen atoms in furan compounds into nitrogen atoms, directly converting them into pyrrole frameworks, which are widely used in pharmaceuticals. < Image. Conceptual image illustrating the main idea of the research > This research was published in the prestigious scientific journal Science on October 3rd under the title "Photocatalytic Furan-to-Pyrrole Conversion." Many drugs have complex chemical structures, but their efficacy is often determined by a single critical atom. Atoms like oxygen and nitrogen play a central role in enhancing the pharmacological effects of these drugs, particularly against viruses. This phenomenon, where the introduction of specific atoms into a drug molecule dramatically affects its efficacy, is known as the "Single Atom Effect." In leading-edge drug development, discovering atoms that maximize drug efficacy is key. However, evaluating the Single Atom Effect has traditionally required multi-step, costly synthesis processes, as it has been difficult to selectively edit single atoms within stable ring structures containing oxygen or nitrogen. Professor Park’s team overcame this challenge by introducing a photocatalyst that uses light energy. They developed a photocatalyst that acts as a “molecular scissor,” freely cutting and attaching five-membered rings, enabling single-atom editing at room temperature and atmospheric pressure—a world first. The team discovered a new reaction mechanism in which the excited molecular scissor removes oxygen from furan via single-electron oxidation and then sequentially adds a nitrogen atom. Donghyeon Kim and Jaehyun You, the study's first authors and candidates in KAIST’s integrated master's and doctoral program in the Department of Chemistry, explained that this technique offers high versatility by utilizing light energy to replace harsh conditions. They further noted that the technology enables selective editing, even when applied to complex natural products or pharmaceuticals. Professor Yoonsu Park, who led the research, remarked, "This breakthrough, which allows for the selective editing of five-membered organic ring structures, will open new doors for building libraries of drug candidates, a key challenge in pharmaceuticals. I hope this foundational technology will be used to revolutionize the drug development process." The significance of this research was highlighted in the Perspective section of Science, a feature where a peer scientist of prominence outside of the project group provides commentary on an impactful research. This research was supported by the National Research Foundation of Korea’s Creative Research Program, the Cross-Generation Collaborative Lab Project at KAIST, and the POSCO Science Fellowship of the POSCO TJ Park Foundation.
2024.10.11 View 1413

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