Improved protein function opens way for new drug development concept

Researchers at Karolinska Institutet and SciLifeLab describe in a study published in Science how they have improved the ability of a protein to repair oxidative DNA damage and created a new protein function. Their innovative technique can lead to improved drugs for diseases involving oxidative stress, such as cancer, Alzheimer’s disease and lung diseases, but the researchers believe it has even greater potential.

Drug development has long been based on finding specific pathogenic proteins and creating treatments that involve blocking these proteins in various ways. However, many diseases are caused by a loss of or decrease in protein function, which cannot be directly targeted by using inhibitors.

Based on a Nobel Prize-winning discovery

In the current study, researchers from Karolinska Institutet improved the function of a protein called OGG1, an enzyme that repairs oxidative DNA damage, implicated in ageing and diseases such as Alzheimer’s disease, cancer, obesity, cardiovascular diseases, autoimmune diseases and lung diseases.

To conduct their research, the group used a method called organocatalysis, a tool developed by Benjamin List and David W.C. MacMillan who were awarded the 2021 Nobel Prize in Chemistry. The method is based on the discovery that small organic molecules can serve as catalysts and induce chemical reactions without themselves being part of the final product.

The researchers examined how such catalyst molecules, previously described by others, bind to OGG1 and affect its function in cells. One of the molecules proved to be of particular interest.

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