生物素醇-5'-AMP的改进合成：对抗菌药物发现的启示
Improved Synthesis of Biotinol-5'-AMP: Implications for Antibacterial Discovery.
作者信息
Tieu William, Polyak Steven W, Paparella Ashleigh S, Yap Min Y, Soares da Costa Tatiana P, Ng Belinda, Wang Geqing, Lumb Richard, Bell Jan M, Turnidge John D, Wilce Matthew C J, Booker Grant W, Abell Andrew D
机构信息
School of Chemistry and Physics, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
School of Molecular and Biomedical Science, University of Adelaide , Adelaide, South Australia 5005, Australia ; Centre for Molecular Pathology, The University of Adelaide , Adelaide, South Australia 5005, Australia.
出版信息
ACS Med Chem Lett. 2014 Dec 11;6(2):216-20. doi: 10.1021/ml500475n. eCollection 2015 Feb 12.
An 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.
报道了一种改进的生物素醇-5'-AMP的合成方法，它是生物素蛋白连接酶（BPL）天然反应中间体的酰基-AMP模拟物。该化合物被证明是一系列具有临床重要性的细菌（特别是金黄色葡萄球菌和结核分枝杆菌）中BPL的泛抑制剂，动力学分析表明它对底物生物素具有竞争性。生物素醇-5'-AMP对一组金黄色葡萄球菌和结核分枝杆菌临床分离株也具有抗菌活性，其MIC值分别为1-8和0.5-2.5μg/mL，同时对人HepG2细胞无细胞毒性。
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