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）：拟议的研究涉及具有出色的生物学活性与革兰氏阳性阳性细菌（包括有问题的抗性病原体）的合成和研究。据信，正在研究的脂质蛋白皮肽抗生素可以通过抑制糖基化反应来表现其生物学活性，这是肽聚糖生物合成途径的关键晚期转化。另外，抑制脂质回收还可能有助于观察到的生物学活性。拟议的研究旨在鉴定用于治疗革兰氏阳性感染的新型化学实体，尤其是由于耐药性革兰氏阳性病原体而引起的感染。