期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 63, 期 23, 页码 14937-14950出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.0c01506
关键词
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资金
- National Research Foundation of Korea [NRF-2017M3A9E4077444]
- Ministry of Health & Welfare (Korea Health Technology RD Project) [HI17C2052, HI20C0189]
- National Research Foundation of Korea [2017M3A9E4077444] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Gram-negative bacteria are becoming resistant to almost all currently available antibiotics. Systemically designed antimicrobial peptides (AMPs) are attractive agents to enhance the activities of antibiotics. We constructed a small Pro-scanning library using amphipathic model peptides. Measurements of minimum inhibitory concentration (MIC) against Escherichia coli and hemolytic activities showed that one of the Pro-hinged peptides, KL-L9P, displays the highest specificity toward E. coli. Moreover, KL-L9P sensitizes E. coli to be responsive to most antibiotics that are not active against Gram-negative bacteria. The results of biochemical experiments show that KL-L9P promotes the rearrangement of the bacterial membrane that enables hydrophobic antibiotics to permeate. Finally, the results of animal tests demonstrate that KL-L9P strongly sensitizes Gram-negative bacteria to linezolid (Lzd), rifampicin (Rif), or clarithromycin (Clr). Thus, KL-L9P operates as a sensitizer to extend the antibacterial activity of most antibiotics to Gram-negative bacteria.
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