Universal barcodes enable fast small molecule synthesis

The development of molecules to study and treat diseases is increasingly burdened by the time and specificity required to analyze the vast amounts of data generated by synthesizing large collections of new molecules. It’s taking place. Scientists at St. Jude Children’s Research Hospital present a new solution to this problem by using basic fragmentation patterns of chemical building blocks to barcode reactions from starting materials to products. I did.

In doing so, they removed a key bottleneck in the process of small molecule synthesis and screening. Their research is published in the journal Nature.

Current analytical methods fall short of the scale of rapid, high-throughput analyzes that researchers desire. St. Jude scientists, led by Dr. Daniel Blair of St. Jude’s School of Chemical Biology and Therapeutics, set out to solve this problem by taking advantage of a common feature present in most chemical reactions.

“Versatility is essential if you want to do anything quickly, so we sought to identify common features that uniformly code the analysis of small molecules,” said Blair, corresponding author of the paper. he explained.

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

Fragmentation-first approach to experimental design

Fragmentation is a fundamental property of chemicals, but this novel application in the field of chemical synthesis gives fragmentation new meaning. The typical time to analyze the results of a chemical reaction has traditionally been about 3 minutes, but that time is decreasing as researchers scale up and analyze additional reactions using more variables. Be realistic.

This work by Blair and his team moves chemical reaction analysis from a time-consuming, highly customized, expert-driven approach to a streamlined approach with easy-to-identify fragmented barcodes and a single analytical readout. will be converted.

“These fragmentation patterns are fundamental properties of chemicals, so they can be reliably transferred from starting materials to products. As soon as we realize that the starting materials can define the analysis of the resulting chemical products, the approach “It generalizes the whole thing,” said lead author Maowei Hu, Ph.D., of St. Jude’s School of Chemical Biology and Therapeutics.

Because this fundamental property is not disease- or specialty-specific, this fragmentation-first approach to high-throughput experimental design can be applied in a variety of ways. Future applications may include the development of antibiotics, antifungals, cancer treatments, molecular adhesives, and many other types of molecules.

“We have not only changed the speed of chemical reaction analysis, but also paved the way for the direct use of these molecules to understand and fight disease,” Blair said.

“This advancement represents a significant milestone in our mission to develop effective treatments quickly and efficiently. We are transforming chemical reaction analysis from minutes to milliseconds, and in doing so , we shifted the bottleneck from creating molecules to discovering their functions.”