Recent advances in chemical proteomics: exploring the post-translational proteome
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REVIEW
Recent advances in chemical proteomics: exploring the post-translational proteome Edward W. Tate
Received: 26 January 2008 / Accepted: 18 February 2008 / Published online: 9 May 2008 # Springer-Verlag 2008
Abstract Identification and quantification of multiple proteins from complex mixtures is a central theme in postgenomic biology. Despite recent progress in high-throughput proteomics, proteomic analysis of post-translationally modified (PTM) proteins remains particularly challenging. This mini-review introduces the emerging field of chemical proteomics and reviews recent advances in chemical proteomic technology that are offering striking new insights into the functional biology of post-translational modification. Keywords Post-translational modification . Phosphorylation . Glycosylation . Lipidation . Chemical proteomics . Site-specific protein labelling
Introduction Identification and quantification of multiple proteins from complex mixtures is a central theme in post-genomic biology. Whilst high-throughput proteomics now enables identification and relative quantification of hundreds to thousands of proteins in a single experiment, significant barriers remain for the analysis of specific protein families of central importance in biology and medicine [1–3]. Proteomic analysis of post-translationally modified (PTM) proteins has proven particularly challenging due to the problems of identifying modified peptides by mass spectrometry and interference from the high background of
E. W. Tate (*) Department of Chemistry, Imperial College London, Exhibition Road, London SW72AZ, UK e-mail: [email protected] URL: http://www3.imperial.ac.uk/people/e.tate
unmodified material. Recent developments in the emerging fields of chemical biology and chemical proteomics [4–8] have resulted in techniques that either take advantage of the cell’s post-translational machinery or exploit subtle differences in the chemical or enzymatic reactivity of specific PTMs to incorporate a small chemical tag specifically at the site of modification. Exquisitely selective chemical reactions can then be used to introduce any combination of secondary labels that enable detection, manipulation and enrichment of proteins bearing a specific PTM [9, 10]. These unique applications of metabolic and protein engineering have opened up a wide range of applications in protein labelling, basic biology, biomarker discovery and drug discovery. This mini-review provides an overview of the techniques available for post-translational chemical proteomics and reviews a selection of key recent advances and applications.
Chemical proteomics: an overview The principle technologies underlying post-translational chemical proteomics are shown in Fig. 1. The key unifying step is the generation of a protein labelled with a small chemical tag at the site of post-translational modification. A highly selective chemical reaction, termed a bioorthogonal ligation, is then performed between the chemical tag and a capture reagent to introduce one or more secondary labe
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