Chemical tools for understanding protein lipidation in eukaryotes.

Lipidation of proteins is an important mechanism to regulate protein trafficking and activity in cell and tissues. The targeting of proteins to membranes by lipidation plays key roles in many physiological processes and when not regulated properly can lead to cancer and neurological disorders. Dissecting the precise roles of protein lipidation in physiology and disease is a major challenge. Recent advances in chemical biology have now enabled the semisynthesis of lipidated proteins for fundamental biochemical and cellular studies. In addition, new chemical reporters of protein lipidation have improved the detection and enabled the proteomic analysis of lipidated proteins. The expanding efforts in chemical biology are therefore providing new tools to dissect the mechanisms and functions of protein lipidation as well as develop therapeutics targeted at protein lipidation pathways in disease.