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Strategies for the chemical construction of synthetic proteins with precisely positioned post-translational modifications or their mimics offer a powerful method for dissecting the complexity of functional protein alteration and the associated complexity of proteomes. | IFEBS Journal REVIEW ARTICLE Chemical approaches to mapping the function of post-translational modifications David P. Gamblin Sander I. van Kasteren Justin M. Chalker and Benjamin G. Davis Chemistry Research Laboratory Department of Chemistry University of Oxford UK Keywords chemoselective ligation post-translational modification protein glycosylation protein modification synthetic proteins Strategies for the chemical construction of synthetic proteins with precisely positioned post-translational modifications or their mimics offer a powerful method for dissecting the complexity of functional protein alteration and the associated complexity of proteomes. Correspondence B. G. Davis Chemistry Research Laboratory 12 Mansfield Road Oxford OX1 3TA UK Fax 44 0 1865 285 002 Tel 44 0 1865 275652 E-mail ben.davis@chem.ox.ac.uk Website http www.chem.ox.ac.uk researchguide bgdavis.html Note Taken in part from Young Investigator Award lecture delivered to the MPSA 2006 meeting in Lille Received 18 July 2007 revised 10 February 2008 accepted 21 February 2008 doi 10.1111 j.1742-4658.2008.06347.x Introduction Post-translational modifications PTMs of proteins modulate protein activity and greatly expand the diversity and complexity of their biological function. The ubiquity of PTMs is reflected in their widespread roles in signaling protein folding localization enzyme activation and protein stability 1-3 . Indeed the prevalence of such modifications in higher organisms such as humans is a leading candidate for the origin of such complex biological functions 4 which may arise from a comparatively restricted genetic code 5-7 . As a consequence of the lack of direct genetic control of their biosynthesis natural PTMs vary in site and level of incorporation leading to mixtures of modified proteins that may differ in function. In order to fully dissect the biological role of PTMs and determine precise structure-activity relationships access to pure protein derivatives is essential. One
