Exploring Peptide Conjugates as Trojan Horse Systems for Drug Design and Discovery

探索肽缀合物作为药物设计和发现的特洛伊木马系统

• 批准号: 9030580
• 负责人: Satish K Nair
• 金额: $ 41.51万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9030580
• 关键词: Active Biological Transport; Affinity; Anabolism; Antibiotics; Antifungal Agents; Appearance; Aspartate-tRNA Ligase; Aspartic Acid-Specific tRNA; Bacteria; Binding; Cells; Cleaved cell; Complex; Conjugated Carrier; Coupled; Data; Development; Drug Design; Engineering; Enterobacteriaceae; Enzymes; Equus caballus; Escherichia coli; Excision; Genes; In Vitro; Knowledge; Ligands; Ligase; Mediating; Modification; Natural Products; Nature; Nucleotides; Oligopeptides; Operon; Organism; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Process; Reaction; Research; Scheme; Siderophores; Specificity; Structure; System; Variant; adenylate; antibiotic design; antimicrobial; bacterial resistance; catalyst; design; drug discovery; in vitro activity; in vivo; inhibitor/antagonist; microcin; nanomolar; novel; pathogen; pathogenic bacteria; phosphoramidate; public health relevance; reconstitution; research study; scaffold; uptake

 DESCRIPTION (provided by applicant): Microcin C7 (McC) is a potent natural product antimicrobial produced by enterobacteria. McC enters the target cell using a "Trojan horse" strategy, in which the active portion of the antibiotic is coupled to a peptide carrier that faciliates import into target cell through active transporters. We have characterized several biosynthetic clusters for that produce the same antibiotic component but with different peptide attachments. Presumably, changes in the peptide allow for import through different transport systems that are specific to different bacterial species. Here we seek to: i. install variations in the peptide carrer allowing the molecule to be taken up by diverse bacteria. ii. re-design the peptide carrier so that it can be more effectively imported into susceptible organisms.

 描述（由申请人提供）：Microcin C7 (McC) 是一种由肠细菌产生的有效天然产物抗菌剂，Mc 使用“特洛伊木马”策略进入靶细胞，其中抗生素的活性部分与肽载体偶联。我们已经表征了几种生物合成簇，它们产生相同的抗生素成分，但具有不同的肽附着物，推测肽的变化允许。在这里，我们寻求： i. 在肽载体中安装变异体，使分子能够被不同的细菌吸收。 它可以更有效地导入易感生物体内。