Chemical biology approaches to probe the proteome

Abstract

Understanding disease-associated cellular defects at a molecular level is critical for the development of pharmacological intervention strategies. Recent breakthroughs in microarray and sequencing technologies have provided powerful tools to rapidly reveal the cellular defects caused by alterations in the genome or transcriptome. However, the picture of how the cellular proteome is affected in a disease state and how changes in DNA and RNA affect protein function is often incomplete. This is perhaps not surprising because the functions of proteins are not just determined by primary sequence and abundance, but are under the control of many regulatory mechanisms. Here, we highlight several recent advances in proteomics technologies that are being developed to generate comprehensive human proteome maps and discuss them in the context of strategies that have been developed in simple model organisms. Chemical biology will play a critical role in drafting a map of the proteome with functional information. Chemical genetic approaches that use high-throughput small molecule screening have resulted in the public availability of small molecule datasets through web interfaces such as PubChem. With such approaches, the opportunities to investigate disease and to explore the proteome with chemistry are rapidly increasing. In addition, new tools are being developed to probe protein function. Here we highlight recent developments in chemical biology and the exciting opportunities that are arising with them.