Abstract |
Poor proteolytic resistance is an urgent problem to be solved in the clinical application of antimicrobial peptides (AMPs), yet common solutions, such as complicated chemical modifications and utilization of d- amino acids, greatly increase the difficulty and cost of producing AMPs. In this work, a set of novel peptides was synthesized based on an antitrypsin/antichymotrypsin hydrolytic peptide structure unit (XYPX) n (X represents I, L, and V; Y represents R and K), which was designed using a systematic natural amino acid arrangement. Of these peptides, 16 with seven repeat units had the highest average selectivity index (GMSI = 99.07) for all of the Gram-negative bacteria tested and remained highly effective in combating Escherichia coli infection in vivo. Importantly, 16 also had dramatic resistance to a high concentration of trypsin/ chymotrypsin hydrolysis and exerted bactericidal activity through a membrane-disruptive mechanism. Overall, these findings provide new approaches for the development of antiprotease hydrolytic peptides that target Gram-negative bacteria.
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Authors | Jiajun Wang, Jing Song, Zhanyi Yang, Shiqi He, Yi Yang, Xingjun Feng, Xiujing Dou, Anshan Shan |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 62
Issue 5
Pg. 2286-2304
(03 14 2019)
ISSN: 1520-4804 [Electronic] United States |
PMID | 30742437
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Antimicrobial Cationic Peptides
- Biocompatible Materials
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Topics |
- Animals
- Anti-Bacterial Agents
(pharmacology)
- Antimicrobial Cationic Peptides
(chemistry, pharmacology)
- Biocompatible Materials
- Gram-Negative Bacteria
(drug effects, ultrastructure)
- HEK293 Cells
- Humans
- Mice
- Microbial Sensitivity Tests
- Microscopy, Electron, Scanning
- Proteolysis
- RAW 264.7 Cells
- Spectrometry, Fluorescence
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