Proteomic Approaches in Drug Discovery and Development

Abstract

This chapter describes the proteomic approaches in drug discovery and development. Proteomics represents the effort to establish the identities, quantities, structures, and biochemical and cellular functions of all proteins in an organism, organ, or organelle and how these properties vary in space, time, or physiological state. The proteome is more complex than the genome, because the inherent biochemical nature of proteins depends on more complicated building blocks. Intracellular localization, proteolytic processing, post-translational modification, and protein-protein interactions add greatly to protein complexity. The chapter provides an overview of the existing technologies, and presents a case study that shows how two-dimensional gel electrophoresis (2DE)-mass spectroscopy (MS) profiling approaches can be applied to one type of issue central to drug discovery and development. From a drug discovery and development perspective, the greatest challenge is translating the information garnered from proteomic initiatives into quantitative, sensitive, and specific assays capable of delivering information about a drug's effect on the target, and if the drug can effectively alter the disease in a clinically beneficial manner. Although proteomics may provide information about new targets, one of the major hurdles in early drug discovery is to demonstrate that the drug has bound specifically to target and produced a biological, meaningful activity both in vitro and in vivo. Despite the existing challenges, proteomic technologies offer powerful tools for difficult scientific questions, and are certainly a path to the future for more efficient drug discovery and development.