New Technique Could Lead to Improved Cancer, Alzheimer’s, and Lung Disease Drugs

In a paper that was published in the journal Science, scientists from Sweden’s Karolinska Institutet and SciLifeLab reveal how they were able to enhance a protein’s ability to repair oxidative DNA damage while also creating a new protein function. The researchers’ ground-breaking technique may result in better treatments for oxidative stress-related illnesses such as cancer, Alzheimer’s, and lung diseases, but they think it has even more potential.

Finding certain pathogenic proteins and developing medicines that inhibiting these proteins has long been the foundation of the drug development process. However, many illnesses are caused by a reduction or loss of protein function, which cannot be specifically targeted by inhibitors.

Inspired by a Nobel Prize-winning discovery

In the current study, scientists from the Karolinska Institutet enhanced the function of the protein OGG1, an enzyme that fixes oxidative DNA damage and is linked to aging and disorders including Alzheimer’s disease, cancer, obesity, cardiovascular diseases, autoimmune disorders, and lung diseases.

The team used a technique called organocatalysis, which was created by Benjamin List and David W.C. MacMillan, who were awarded the 2021 Nobel Prize in Chemistry. The process is based on the finding that tiny organic molecules have the ability to function as catalysts and start chemical processes without becoming a component of the end result.

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.

Ten times more effective

“When we introduce the catalyst into the enzyme, the enzyme becomes ten times more effective at repairing oxidative DNA damage and can perform a new repair function,” says the study’s first author Maurice Michel, assistant professor at the Department of Oncology-Pathology, Karolinska Institutet.

The catalyst made it possible for the enzyme to cut the DNA in an unusual way so that it no longer requires its regular protein APE1 to work but another protein called PNKP1.