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1. 发明申请

WO2012036907A2 BROAD SPECTRUM ANTIBIOTIC ARYLOMYCIN ANALOGS 审中-公开
标题翻译： BROAD SPECTRUM抗生素ARYLOMYCIN模拟
公开(公告)号：WO2012036907A2
公开(公告)日：2012-03-22
申请号：PCT/US2011/049967
申请日：2011-08-31
申请人： ROMESBERG, Floyd E. , SMITH, Peter A. , ROBERTS, Tucker C.
发明人： ROMESBERG, Floyd E. , SMITH, Peter A. , ROBERTS, Tucker C.
IPC分类号： C07K5/12
CPC分类号： C07K7/06 , A61K38/00 , A61K38/08 , A61K38/14 , A61K45/06 , C07K9/001 , Y02A50/47 , Y02A50/471 , Y02A50/473 , Y02A50/475 , Y02A50/481
摘要： Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.
摘要翻译：提供了芳香霉素类似物，其中类似物可具有广谱生物活性。已经发现天然产物芳香霉素在一系列病原菌种中对抗生素生物活性的抗性取决于在细菌信号肽酶（SPases）的限定位置上的单个氨基酸突变，其中脯氨酸残基的存在赋予芳樟霉素抗性。本文提供的芳香霉素类似物可以克服该抗性，并提供比天然产物芳香霉素如芳香霉素A2更广谱的抗生素生物活性。提供了确定细菌菌株是否易受窄谱芳香霉素抗生素敏感的方法，或者如果需要宽谱类似物进行治疗。提供了治疗细菌感染的药物组合物和方法，以及合成法罗霉素类似物的方法。

2. 发明申请

WO2012036907A3 BROAD SPECTRUM ANTIBIOTIC ARYLOMYCIN ANALOGS 审中-公开
标题翻译：广谱抗生素阿糖胞苷类似物
公开(公告)号：WO2012036907A3
公开(公告)日：2012-08-09
申请号：PCT/US2011049967
申请日：2011-08-31
申请人： ROMESBERG FLOYD E , SMITH PETER A , ROBERTS TUCKER C
发明人： ROMESBERG FLOYD E , SMITH PETER A , ROBERTS TUCKER C
IPC分类号： A61K38/04 , A61K38/12
CPC分类号： C07K7/06 , A61K38/00 , A61K38/08 , A61K38/14 , A61K45/06 , C07K9/001
摘要： Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.
摘要翻译：提供了一种芳基霉素类似物，其中类似物可以具有广谱的生物活性。已经发现对一系列致病细菌物种中的天然产物arylomycin的抗生素生物活性的抗性取决于细菌信号肽酶（SPase）的限定位置处的单个氨基酸突变，其中脯氨酸残基的存在赋予arylomycin抗性。本文提供的芳基霉素类似物可以克服该抗性并提供比天然产物arylomycin如arylomycin A2更广谱的抗生素生物活性。提供了用于确定细菌菌株是否对窄谱arylomycin抗生素敏感的方法，或者如果需要广谱的类似物用于治疗的方法。提供了药物组合物和治疗细菌感染的方法以及合成arylomycin类似物的方法。

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