翻译：硫醚稳定肽的翻译后细菌展示和筛选。
Bacterial display and screening of posttranslationally thioether-stabilized peptides.
机构信息
LanthioPep, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
出版信息
Appl Environ Microbiol. 2011 Oct;77(19):6794-801. doi: 10.1128/AEM.05550-11. Epub 2011 Aug 5.
Abstract
A major hurdle in the application of therapeutic peptides is their rapid degradation by peptidases. Thioether bridges effectively protect therapeutic peptides against breakdown, thereby strongly increasing bioavailability, enabling oral and pulmonary delivery and potentially significantly optimizing the receptor interaction of selected variants. To efficiently select optimal variants, a library of DNA-coupled thioether-bridged peptides is highly desirable. Here, we present a unique cell surface display system of thioether-bridged peptides and successfully demonstrate highly selective screening. Peptides are posttranslationally modified by thioether bridge-installing enzymes in Lactococcus lactis, followed by export and sortase-mediated covalent coupling to the lactococcal cell wall. This allows the combinatorial optimization and selection of medically and economically highly important therapeutic peptides with strongly enhanced therapeutic potential.
摘要
治疗性肽的应用面临的一个主要障碍是其被肽酶迅速降解。硫醚键可有效地保护治疗性肽免受破坏，从而大大提高生物利用度，实现口服和肺部给药，并有可能显著优化所选变体的受体相互作用。为了有效地选择最佳变体，高度需要构建包含 DNA 偶联硫醚键的肽文库。在这里，我们提出了一种独特的硫醚键连接肽的细胞表面展示系统，并成功地展示了高度选择性的筛选。肽在乳球菌中由硫醚桥安装酶进行翻译后修饰，然后通过外排和连接酶介导的共价偶联到乳球菌细胞壁上。这使得可以对具有显著增强的治疗潜力的具有医学和经济重要性的治疗性肽进行组合优化和选择。
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