Exploring the active core of a novel antimicrobial peptide, palustrin-2LTb, from the Kuatun frog, Hylarana latouchii, using a bioinformatics-directed approach.

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 , 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 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.