Optimising in situ click chemistry: the screening and identification of biotin protein ligase inhibitors

Abstract

A 'leaky mutant' (SaBPL-R122G) of Staphylococcus aureus biotin protein ligase (SaBPL) is used to enhance the turnover rate for the reaction of biotin alkyne with an azide to give a triazole. This allows the enzyme to select the optimum triazole-based inhibitor using a library of such azides in a single experiment with greatly improved efficiency and sensitivity of detection, difficulties that can restrict the general utility of a multi-component in situ click approach to ligand optimisation. © 2013 The Royal Society of Chemistry.William Tieu, Tatiana P. Soares da Costa, Min Y. Yap, Kelly L. Keeling, Matthew C. J. Wilce, John C. Wallace, Grant W. Booker, Steven W. Polyak and Andrew D. Abel