The bogorol family of antibiotics: Template-based structure elucidation and a new approach to positioning enantiomeric pairs of amino acids
The bogorol family of antibiotics: Template-based structure elucidation and a new approach to positioning enantiomeric pairs of amino acids
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DOI：
10.1021/jo060667p
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发表时间：
2006-08-04
影响因子：
3.6
通讯作者：
Andersen, Raymond J.
中科院分区：
文献类型：
--
作者：
Barsby, Todd;Warabi, Kaoru;Andersen, Raymond J.
bogorol A(1)中D和L Leu和Lys残基的序列位置已通过一种简单而新颖的方法确定，该方法利用少量样品，重点检测酸催化水解过程中氨基酸从母体肽中释放的顺序。这项技术建立在先前建立的氨基酸的空间和电子特征与它们通过二肽从多肽中酸性解放的偏好之间的关系之上。这一结果完成了bogorol A的结构，并得到了传统降解实验的证实。利用bogorols A(1)的结构知识作为模板，通过ESI-MS和ESI-MS/ MS数据分析以及降解产物的GC分析，我们快速阐明了bogorols B-E（2-5）的结构。bogorol阳离子肽抗生素含有许多不寻常的结构特征，包括c端残基还原为缬氨酸，n端残基还原为2-羟基-3-甲基戊酸，四个D氨基酸的结合，以及脱氢氨基酸的存在。Bogorols对耐甲氧西林金黄色葡萄球菌和耐万古霉素肠球菌具有选择性和相对有效的活性，对大肠杆菌具有中等活性。
The sequence positions of D and L Leu and Lys residues in bogorol A (1) have been defined by a simple and novel approach that utilizes small amounts of sample and focuses on detecting the order in which amino acids are liberated from the parent peptide during acid-catalyzed hydrolysis. This technique builds on a previously established relationship between the steric and electronic features of amino acids and their predilection for acidic liberation from polypeptides via dipeptides. The results, which complete the structure of bogorol A, have been confirmed by traditional degradation experiments. Utilizing the knowledge of the structure of bogorol A (1) as a template, we rapidly elucidated the structures of bogorols B-E (2-5) via analysis of ESI-MS and ESI-MS/ MS data and GC analysis of degradation products. The bogorol cationic peptide antibiotics contain a number of unusual structural features, which include the reduction of the C-terminal residue to valinol, an N-terminal residue of 2-hydroxy-3-methylpentanoic acid, the incorporation of four D amino acids, and the presence of a dehydroamino acid. Bogorols show selective and relatively potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp., as well as moderate activity against Escherichia coli.