New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

Jiage Feng; Ashleigh S Paparella; William Tieu; David Heim; Sarah Clark; Andrew Hayes; Grant W Booker; Steven W Polyak; Andrew D Abell

doi:10.1021/acsmedchemlett.6b00248

New Series of BPL Inhibitors To Probe the Ribose-Binding Pocket of Staphylococcus aureus Biotin Protein Ligase

ACS Med Chem Lett. 2016 Oct 10;7(12):1068-1072. doi: 10.1021/acsmedchemlett.6b00248. eCollection 2016 Dec 8.

Authors

Jiage Feng¹, Ashleigh S Paparella¹, William Tieu¹, David Heim¹, Sarah Clark¹, Andrew Hayes¹, Grant W Booker¹, Steven W Polyak¹, Andrew D Abell¹

Affiliation

¹ Department of Chemistry, Department of Molecular and Cellular Biology, and Centre for Nanoscale BioPhotonics (CNBP), University of Adelaide , Adelaide, South Australia 5005, Australia.

Abstract

Replacing the labile adenosinyl-substituted phosphoanhydride of biotinyl-5'-AMP with a N1-benzyl substituted 1,2,3-triazole gave a new truncated series of inhibitors of Staphylococcus aureus biotin protein ligase (SaBPL). The benzyl group presents to the ribose-binding pocket of SaBPL based on in silico docking. Halogenated benzyl derivatives (12t, 12u, 12w, and 12x) proved to be the most potent inhibitors of SaBPL. These derivatives inhibited the growth of S. aureus ATCC49775 and displayed low cytotoxicity against HepG2 cells.

Keywords: Enzyme inhibitors; Staphylococcus aureus; antibiotics; biotin protein ligase.