[EN] BROAD SPECTRUM ANTIBIOTIC ARYLOMYCIN ANALOGS<br/>[FR] ANALOGUES DE L'ARYLOMYCINE À SPECTRE ANTIBIOTIQUE LARGE
申请人:SCRIPPS RESEARCH INST
公开号:WO2013138187A1
公开(公告)日:2013-09-19
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.
提供了芳基霉素类似物,其中这些类似物可以具有广谱生物活性。已发现在一系列致病性细菌物种中,对天然产物芳基霉素的抗生素活性的抗性取决于细菌信号肽酶(SPases)的特定位置的单个氨基酸突变,其中脯氨酸残基的存在赋予了芳基霉素抗性。本文提供了可以克服该抗性并提供比芳基霉素A2等天然产物芳基霉素更广谱抗生素活性的芳基霉素类似物。提供了用于确定细菌菌株是否对窄谱芳基霉素抗生素敏感,或者是否需要广谱类似物进行治疗的方法。提供了用于治疗细菌感染的药物组合物和方法,以及芳基霉素类似物的合成方法。