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Antimicrobial peptides show great potential as new antibiotics. However, a major obstacle to the development of these peptides as useful drugs is their low stability. To overcome the problem of the natural antimicrobial peptide <jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>\u2010C1, we designed and synthesized a series of analogs. Our results indicated that by introducing lysine, which could increase the number of positive charges, and by introducing tryptophan, which could increase the hydrophobicity, we could improve the antimicrobial activity of the peptides against multidrug\u2010resistant strains. The introduction of <jats:sc>d<\/jats:sc>\u2010amino acids significantly improved stability. Certain analogs demonstrated antibiofilm activities. In mechanistic studies, the analogs eradicated bacteria not just by interrupting the bacterial membranes, but also by linking to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>, which was not impacted by known mechanisms of resistance. In a mouse model, certain analogs were able to significantly reduce the bacterial load. Among the analogs, <jats:styled-content style=\"fixed-case\">CPF<\/jats:styled-content>\u20109 was notable due to its greater antimicrobial potency in vitro and in vivo and its superior stability, lower hemolytic activity, and higher antibiofilm activity. This analog is a potential antibiotic candidate for treating infections induced by multidrug\u2010resistant bacteria.<\/jats:p>","DOI":"10.1111\/cbdd.12988","type":"journal-article","created":{"date-parts":[[2017,3,29]],"date-time":"2017-03-29T14:55:28Z","timestamp":1490799328000},"page":"690-702","source":"Crossref","is-referenced-by-count":45,"title":["Novel antimicrobial peptide <scp>CPF<\/scp>\u2010C1 analogs with superior stabilities and activities against multidrug\u2010resistant bacteria"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4808-7307","authenticated-orcid":false,"given":"Junqiu","family":"Xie","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"},{"name":"Key Laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences Lanzhou University  Lanzhou 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