首页|Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide

Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide

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The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action.In this study, we synthesized a novel type of antimicrobial agent, Acr3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence (NLS), a short cationic peptide.To further improve the antimicrobial activity of our agent, dimeric (Acr3-NLS)2 was simultaneously synthesized by joining two monomeric Acr3-NLS together via a disulfide linker.Our results show that Acr3-NLS and especially (Acr3-NLS)2 display significant antimicrobial activity against gramnegative and gram-positive bacteria compared to that of the NLS.Subsequently, the results dedved from the study on the mechanism of action demonstrate that Acr3-NLS and (Acr3-NLS)2 can kill bacteria by membrane disruption and DNA binding.The double targets—cell membrane and intracellular DNA—will reduce the risk of bacteria developing resistance to Acr3-NLS and (Acr3-NLS)2.Overall, this study provides a novel strategy to design highly effective antimicrobial agents with a dual mode of action for infection treatment.

acridinenuclear localization sequenceconjugateantimicrobial activitymechanism of action

Wei Zhang、Xiaoli Yang、Jingjing Song、Xin Zheng、Jianbo Chen、Panpan Ma、Bangzhi Zhang

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Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000,China

Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China

We are grateful for the grants from the National Natural Science Foundation of ChinaWe are grateful for the grants from the National Natural Science Foundation of ChinaKey National S&T Program "Major New Drug Development" of the Ministry of Science and Technology of ChinaFundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central UniversitiesSpecialized Research Fund for the Doctoral Program of Higher Education of ChinaChina Postdoctoral Science Foundation

81402776812024002012ZX09504-001-003lzujbky-2014-142lzujbky-2015-169201302111300052013T60896

2015

10.15302/J-ENG-2015106

工程科学(英文版)
中国工程院出版委员会

工程科学(英文版)

影响因子：0.226
ISSN：1672-4178
年,卷(期)：2015.1(4)
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