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

 说明(申请人提供)：微菌素C7(MCC)是一种由肠道细菌产生的有效的天然抗菌剂。MCC通过一种“特洛伊木马”策略进入靶细胞，在该策略中，抗生素的活性部分与多肽载体偶联，该载体可通过活性转运蛋白方便地进入靶细胞。我们已经表征了几个生物合成的簇，这些簇产生相同的抗生素成分，但具有不同的多肽连接。据推测，多肽的变化允许通过针对不同细菌物种的不同运输系统进行输入。在这里，我们寻求：1.在多肽载体中安装不同的变种，使分子能够被不同的细菌吸收。二、重新设计多肽载体，以便 它可以更有效地输入到易感生物中。

 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.