Antimicrobial peptides (AMPs), one of the most promising next-generation antibiotics to address the problem of antibiotic-resistance, have gained increasing attention in recent decades. However, some bottlenecks, such as high manufacturing costs and high toxicity, have greatly hindered their development. To overcome these problems, we developed an efficient modification approach to find the valid active-core fragments of AMPs by mimicking the cleavage process of trypsin-like specificity proteases in silico, and truncating the peptide. Herein, we used the structure of a novel AMP, palustrin-2LTb, as the template and synthesised a set of interceptive peptides using computer-aided design and prediction. Functional screening data indicated that truncated fragment 3 not only maintained and optimised antimicrobial efficacy of the parent peptide but also showed great in vivo therapeutic potential in an MRSA-infected insect larvae model. Overall, the demonstration of the therapeutic efficacy of fragment 3 showcases the efficiency of our approach for future modification of AMPs.

中文翻译：

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使用生物信息学指导的方法探索来自 Kuatun 青蛙 Hylarana latouchii 的新型抗菌肽 palustrin-2LTb 的活性核心。

近几十年来，抗菌肽 (AMP) 是最有希望解决抗生素耐药性问题的下一代抗生素之一，受到越来越多的关注。然而，制造成本高、毒性大等瓶颈极大地阻碍了其发展。为了克服这些问题，我们开发了一种有效的修饰方法，通过在计算机模拟胰蛋白酶样特异性蛋白酶的切割过程并截短肽来找到 AMP 的有效活性核心片段。在此，我们使用新型 AMP 的结构 palustrin-2LTb 作为模板，并使用计算机辅助设计和预测合成了一组拦截肽。功能筛选数据表明，截短片段 3 不仅保持和优化了母肽的抗菌功效，而且在 MRSA 感染的昆虫幼虫模型中显示出巨大的体内治疗潜力。总的来说，片段 3 的疗效证明展示了我们未来修改 AMP 的方法的效率。