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Taking the chemical out of chemical genetics

Nature Chemical Biology volume 5, pages 609–610 (2009)Cite this article

Screening a library of expressed cyclic peptides identified clones that reverse the cytotoxicity of α-synuclein in yeast and Caenorhabditis elegans. The results suggest a new approach for intervention in Parkinson's disease, and perhaps a druggable target.

The current pharmacopeia of US Food and Drug Administration–approved therapeutics target less than 2% of the open reading frames in the human genome1, and the rate of discovery for drugs that act on new targets has been flat or trending downward for the last two decades2. New and better approaches to interrogate biological systems with small-molecule probes are needed to better define the druggable genome—particularly approaches that engage more scientists from diverse backgrounds in the discovery process. In this issue, Kritzer et al.3 describe a biological approach to forward chemical genetics based on expressed libraries of backbone cyclic peptides in yeast and C. elegans that could be replicated readily in the laboratories of most biomedical scientists.

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Figure 1: Arrayed versus expressed chemical genetics.

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Authors and Affiliations

  1. Charles P. Scott is in the Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. cscott@mail.jci.tju.edu,

    Charles P Scott

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  1. Charles P Scott
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Competing interests

C.P.S. is an inventor on US patent 7,354,756 entitled "Intein mediated cyclization of peptides."

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Scott, C. Taking the chemical out of chemical genetics. Nat Chem Biol 5, 609–610 (2009). https://doi.org/10.1038/nchembio0909-609

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  • DOI: https://doi.org/10.1038/nchembio0909-609

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