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

 描述（由申请人提供）：Microcin C7（McC）是一种由肠杆菌产生的强效天然产物抗菌剂。McC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，该肽载体通过活性转运蛋白促进输入靶细胞。我们已经表征了几种生物合成簇，其产生相同的抗生素组分，但具有不同的肽附件。据推测，肽的变化允许通过不同的转运系统输入，这些转运系统对不同的细菌物种具有特异性。在这里，我们寻求：一。在肽载体上安装变异，使分子被不同的细菌吸收。二.重新设计肽载体， 它可以更有效地输入到易感生物体中。

 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.