Reverse chemical proteomics

Piggott AM, Karuso P. (2008) Rapid identification of a protein binding partner for the marine natural product kahalalide F by using reverse chemical proteomics. ChemBioChem 9 524-530. 

Taken together, in vitro display of cDNA libraries are an integral part of modern reverse chemical proteomics applications, where the goal is to functionally display all proteins and to minimize selection bias in the identification of protein ligands for natural products. 

Piggott, A. M., Karuso, P. (2005). Quality, not quantity the role of marine natural products in drug discovery and reverse chemical proteomics. Mar. Drugs, 3, 36-63. 

Of the approaches listed above the last two (chemical proteomics and ABPP) are currently receiving the most interest and have complementary fields of applications. The affinity-based approach is perfectly suitable for reversible inhibitors, but is limited to quite strong binders. The focus of this chapter will be on the other of these two approaches, namely the activity-based approach to natural product identification. An essential requirement for this approach is that the natural product of investigation contains a reactive functional group that reacts with the protein target, forming a covalent bond. Fortunately, a considerable number of natural products contain such reactive groups [19]. Mostly, electrophilic moieties such as epoxides, Michael acceptors, disulfides, lactones, (3-lactams, quinones, etc. can be found. 

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