Novel Inhibitors of Peptidoglycan Biosynthesis Targeting Gram-positive Pathogens

针对革兰氏阳性病原体的新型肽聚糖生物合成抑制剂

• 批准号: 8913230
• 负责人: Michael S VanNieuwenhze
• 金额: $ 34.71万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8913230
• 关键词: Address; Affinity; Anabolism; Antibiotics; Bacteria; Binding; Binding Sites; Biochemical; Biological; Cell Wall; Cells; Chemicals; Collaborations; Complex; Data; Depsipeptides; Development; Evaluation; Glycopeptide Antibiotics; Glycopeptides; Health; Infection; Investigation; Label; Lactams; Letters; Lipids; Maps; Measurement; Molecular Conformation; Molecular Target; Pathway interactions; Peptides; Peptidoglycan; Pharmaceutical Preparations; Positioning Attribute; Proline; Public Health; Reaction; Recycling; Research; Resistance; Series; Sodium Chloride; Solutions; Staging; Staphylococcus aureus; Structure; Structure-Activity Relationship; Therapeutic Agents; Ursidae Family; Vancomycin; analog; bacterial resistance; base; chemical synthesis; chemotherapeutic agent; computer studies; empedopeptin; inhibitor/antagonist; insight; interest; molecular dynamics; novel; pathogen; plusbacin A3; professor; research study; response; scaffold; screening; solid state; three dimensional structure; tool

DESCRIPTION (provided by applicant): The proposed research involves synthesis and study of lipodepsipeptide antibiotics that possess excellent biological activity versus Gram-positive positive bacteria, including problematic resistant pathogens. The lipodepsipeptide antibiotics under study are believed to manifest their biological activity through inhibition of the transglycosylation reaction, a key late stage transformation in the peptidoglycan biosynthetic pathway. In addition, the inhibition of lipid recycling may also contribute to the observed biological activity. The proposed research seeks to identify novel chemical entities to be used for the treatment of Gram-positive infections and, in particular, infections due to problematic resistant Gram-positive pathogens.

描述（由申请人提供）：拟议的研究涉及脂缩肽抗生素的合成和研究，这些抗生素对革兰氏阳性细菌（包括有问题的耐药病原体）具有优异的生物活性。据信，正在研究的脂缩肽抗生素通过抑制转糖基反应（肽聚糖生物合成途径的关键后期转化）来显示其生物活性。此外，脂质循环的抑制也可能有助于观察到的生物活性。拟议的研究旨在确定用于治疗革兰氏阳性感染的新型化学实体，特别是由有问题的耐药革兰氏阳性病原体引起的感染。