New tool accelerates drug discovery

By Rachel Paul on February 6, 2025

Drug Discovery with new tool – The time and specificity necessary to examine the massive amounts of data created by synthesizing big collections of novel molecules is putting a strain on the production of molecules for disease research and treatment. Scientists at St. Jude Children’s Research Hospital have proposed an innovative solution to this problem: use the fundamental fragmentation patterns of chemical building blocks to barcode reactions from starting materials to products. In doing so, they reduced a critical bottleneck in the synthesis and screening of tiny compounds. The findings were published today in Nature.

Current analytical methods fall short of researchers’ expectations for quick, high-throughput analysis. Scientists at St. Jude, lead by Daniel Blair, PhD, St. Jude Department of Chemical Biology and Therapeutics, set out to solve this problem by leveraging a common property found in most chemical processes.

“Generality is essential for doing anything quickly. So, we sought to identify general features which would uniformly encode the analysis of small molecules,” explained Blair, corresponding author of the Nature article.

We discovered that the building blocks we use to create small molecules break apart in specific, predictable ways and that these patterns can then be used as universal barcodes to analyze chemical products.”

Daniel Blair, St. Jude Children’s Research Hospital

A fragmentation-first approach to experimental design

Fragmentation is a core property of chemical matter, but its new use in synthesis adds importance. Analyzing a chemical reaction typically takes about 3 minutes. However, scaling up to study more reactions with more variables makes this time unworkable. Blair and his team simplify this process. They transform reaction analysis from slow and specialist-driven to a fast method. It uses clear fragmentation barcodes and a single analytical output.

“Because these fragmentation patterns are a fundamental property of chemical matter, they are reliably transposable from starting materials to products. As soon as you recognize that starting materials can define the analysis of the resulting chemical products, you’ve generalized the entire approach,” said first author Maowei Hu, PhD, St. Jude Department of Chemical Biology and Therapeutics.

This fragmentation-first approach to high-throughput experimental design can be used in a variety of ways because this underlying trait is neither disease- or discipline-specific. Future applications could include the creation of antibiotics, antifungals, cancer therapies, molecular glues, and a variety of other compounds.

“We’ve not only transformed the speed of chemical reaction analysis but also paved the way for directly utilizing these molecules to understand and combat diseases,” said Blair. “This advance represents a significant milestone in our mission to develop effective therapies swiftly and efficiently. We’ve transformed chemical reaction analysis from minutes to milliseconds, and in doing so, have shifted the bottleneck from making molecules to finding functions.”

For more information: Hu, M., et al. (2024) Continuous collective analysis of chemical reactions. Nature. doi.org/10.1038/s41586-024-08211-4.

Rachel Paul

Rachel Paul is a Senior Medical Content Specialist. She has a Masters Degree in Pharmacy from Osmania University. She always has a keen interest in medical and health sciences. She expertly communicates and crafts latest informative and engaging medical and healthcare narratives with precision and clarity. She is proficient in researching, writing, editing, and proofreading medical content and blogs.