Pharmaceutical Research World’s First Atomic Editing Changes the Paradigm of Drug Discovery

In a pioneering advance for drug development, scientists at the Korea Advanced Institute of Science & Technology (Kaist) have developed a pioneering technology that enables the precise and rapid editing of key atoms responsible for drug efficacy.

Kaist announced that Professor Yoonsu Park’s research team from the Department of Chemistry has successfully created single-atom editing technology, marking the first time such a feat has been accomplished. The new technology focuses on converting oxygen atoms in furan compounds into nitrogen atoms, a process that transforms these molecules into pyrrole frameworks — structures commonly used in the creation of pharmaceuticals.

The efficacy of many drugs is influenced by their complex chemical structures, where a single atom can play a decisive role. Atoms like oxygen and nitrogen are especially critical in enhancing the pharmacological effects of drugs, particularly those targeting viral infections. This phenomenon, known as the Single Atom Effect, demonstrates how altering specific atoms within a molecule can dramatically affect a drug's effectiveness.

Historically, evaluating the Single Atom Effect has been a challenging task, requiring laborious and expensive multi-step synthesis processes. The difficulty lies in selectively editing individual atoms within stable chemical structures, such as rings containing oxygen or nitrogen.

Professor Park’s team, however, has overcome these limitations through the introduction of a novel photocatalyst that harnesses light energy. This photocatalyst, described as a "molecular scissor," allows for precise editing of five-membered rings by selectively removing oxygen and inserting nitrogen atoms. Crucially, this process can be performed at room temperature and under normal atmospheric conditions—an unprecedented achievement in the field.

The team uncovered a new reaction mechanism in which the excited molecular scissor removes oxygen from furan compounds via single-electron oxidation, followed by the sequential addition of a nitrogen atom. This discovery opens up new possibilities for drug development, as it simplifies the modification of molecules used in pharmaceuticals and natural products.

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.

Original Article: Photocatalytic furan-to-pyrrole conversion; Science; DOI:10.1126/science.adq6245

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