Initiative for Chemical Genetics

Tolliday, N. et al. 2006. Small molecules, big players the National Cancer Institute s Initiative for Chemical Genetics. Cancer Res. 66, 8935-8942. 

Collaborative research initiatives for the use of chemical genetics to facilitate discovery of potential cancer (or other) therapeutics by the initiative for Chemical Genetics at the National Cancer Institute (50) and to facilitate the discovery of netv targets and drug candidates by the Chemical Genomics Center at the National Institutes of Health (51) have been initiated. These initiatives will result in databases that contain information that most likely will be valuable to the study of cellular signaling networks. 

In eukaryotes, translation initiation is rate-limiting with much regulation exerted at the ribosome recruitment and ternary complex (elF2 GTP Met-tRNAjMet) formation steps. Although small molecule inhibitors have been extremely useful for chemically dissecting translation, there is a dearth of compounds available to study the initiation phase in vitro and in vivo. In this chapter, we describe reverse and forward chemical genetic screens developed to identify new inhibitors of translation. The ability to manipulate cell extracts biochemically, and to compare the activity of small molecules on translation of mRNA templates that differ in their factor requirements for ribosome recruitment, facilitates identification of the relevant target. 

Fig. 6-17 Forward chemical-genetic screen compound activity from the initial cell-based for inhibitors of mitosis (data from Ref. 73). and in vitro tubulin polymerization assay.

Peeler, J.C., et al. 2010. Genetically encoded initiator for polymer growth from proteins. Journal of the American Chemical Society 132(39) 13575-13577. 

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