Innovative approach reveals protein drug targets

Enhanced mapping of small-molecule interactions within cells.

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Researchers at Scripps Research in La Jolla, CA, have created a new method to study how proteins interact with drug-like molecules in human cells. This breakthrough, published in Nature Chemical Biology on January 2, 2024, helps identify ways to target proteins involved in human diseases. Researchers aim to develop more precise and effective therapeutics for various conditions by understanding these interactions.

Associate professor of the Department of Chemistry Christopher Parker, Ph.D., senior author of the study, said, “Our new technology could be used to find new druggable sites on proteins for any human disease, from cancer to Alzheimer’s disease. We’re unrestricted in how this could be used. Our work has the potential to usher in a whole new way of drug discovery.”

The Parker lab at Scripps Research works to understand how proteins function in all human cell types, aiming to develop effective therapies for various diseases. This study improved a method to examine protein interactions with small molecules in living cells. Using photoaffinity probes activated by light, they discovered over a thousand new binding sites on proteins, uncovering new places and shapes for small-molecule connections. This innovative approach enhances our understanding of protein functions, paving the way for more targeted and effective therapeutic development.

Jacob M. Wozniak is the co-first author and former postdoctoral fellow in the Parker lab. The paper’s other co-first author was Weichao Li, Ph.D., a research associate also in the Parker lab who said, “Identifying these specific binding sites will help scientists design new molecules that fit these pockets even better, potentially leading to more effective therapeutics.”

In collaboration with Dr. Stefano Forli, the study’s data was used to model how molecules bind to proteins. This information can help design more precise therapeutics. The researchers aim to apply this technology to target proteins related to autoimmune diseases and cancer for further discovery and intervention.

Journal reference:

  1. Wozniak, J.M., Li, W., Governa, P. et al. Enhanced mapping of small-molecule binding sites in cells. Nature Chemical Biology. DOI: 10.1038/s41589-023-01514-z.

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