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Grand Challenge Commentary: Beyond discovery: probes that see, grab and poke

Nature Chemical Biology volume 6, pages 868–870 (2010)Cite this article

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Chemical biology is now able to discover molecules that manipulate virtually any biological target or process. It remains a grand challenge to leverage these molecules into useful probes that can be used to address unsolved problems in biology.

It happened quite suddenly. I was following an interest in protein folding, and one day I looked up and realized that I was the only chemist in a genetics lab. This led to many patient conversations in which I would learn the difference between epistasis and complementation or I would explain the difference between a lactam and a lactone. However, once we overcame the language barrier, it became clear that my chemical biology approach was seen as a valuable and complementary method for exploring protein folding in the cell. Others in the lab might generate new mutant strains to analyze protein function, whereas I would devise a screen to isolate an inhibitor, but we'd both reach the same ultimate goal. Many other young chemists have had similar opportunities to apply chemical approaches in biomedical research environments, and our experiences show how widely accepted chemical biology has become as an independent approach to studying living systems. This acceptance is reassuring, but it also raises the pressure to deliver on one of chemical biology's central promises: to generate truly useful chemical probes for any cellular target or pathway. For chemical biologists, this represents a grand challenge to consistently reach beyond discovery into the development and application of probes, to ensure that new molecules can be used to answer mechanistic biological questions.

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Figure 1: The probe development challenge.
Figure 2: A few general methods for probe development.

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  1. Joshua A. Kritzer is in the Department of Chemistry, Tufts University, Medford, Massachusetts, USA.,

    Joshua A Kritzer

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Correspondence to Joshua A Kritzer.

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Kritzer, J. Grand Challenge Commentary: Beyond discovery: probes that see, grab and poke. Nat Chem Biol 6, 868–870 (2010). https://doi.org/10.1038/nchembio.469

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