Tieu, W.Polyak, S.Paparella, A.Yap, M.Soares Da Costa, T.Ng, B.Wang, G.Lumb, R.Bell, J.Turnidge, J.Wilce, M.Booker, G.Abell, A.2015-06-182015-06-182015ACS Medicinal Chemistry Letters, 2015; 6(2):216-2201948-58751948-5875http://hdl.handle.net/2440/92379An improved synthesis of biotinol-5'-AMP, an acyl-AMP mimic of the natural reaction intermediate of biotin protein ligase (BPL), is reported. This compound was shown to be a pan inhibitor of BPLs from a series of clinically important bacteria, particularly Staphylococcus aureus and Mycobacterium tuberculosis, and kinetic analysis revealed it to be competitive against the substrate biotin. Biotinol-5'-AMP also exhibits antibacterial activity against a panel of clinical isolates of S. aureus and M. tuberculosis with MIC values of 1-8 and 0.5-2.5 μg/mL, respectively, while being devoid of cytotoxicity to human HepG2 cells.enCopyright © 2014 American Chemical SocietyAntibioticsenzyme inhibitorsbiotin protein ligasechemical synthesisdrug designJournal article003002302310.1021/ml500475n0003496520000202-s2.0-84922876196173713Tieu, W. [0000-0002-7161-4152]Polyak, S. [0000-0002-8458-5194]Soares Da Costa, T. [0000-0002-6275-7485]Turnidge, J. [0000-0003-4240-5578]Booker, G. [0000-0001-7207-4699]Abell, A. [0000-0002-0604-2629]