Single-Atom Editing

New technology that enables the easy and rapid editing of key atoms responsible for drug efficacy

In a major breakthrough for drug development, researchers at KAIST have unveiled a revolutionary technology that allows for precise, rapid editing of individual atoms critical to a drug's effectiveness. This cutting-edge advancement, often referred to as a "dream" technology in the field, promises to transform how potential drug candidates are discovered and optimized, offering a new level of control in enhancing 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.

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."