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Tytuł:
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Identification of New Nitric Oxide-Donating Peptides with Dual Biofilm Eradication and Antibacterial Activities for Intervention of Device-Related Infections.
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Autorzy:
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Fei Y; Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Wu J; Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
An HW; Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Yuquan Road, Beijing 100049, China.
Zhu K; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Peng B; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Cai J; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Zhang Y; Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
Li LL; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Wang H; CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beiyitiao No.11, Haidian District, Beijing, 100190, China.
Huang Z; Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China.
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Źródło:
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Journal of medicinal chemistry [J Med Chem] 2020 Sep 10; Vol. 63 (17), pp. 9127-9135. Date of Electronic Publication: 2020 Aug 18.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Washington Dc : American Chemical Society
Original Publication: [Easton, Pa.] : American Chemical Society, [c1963-
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MeSH Terms:
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Anti-Bacterial Agents/*pharmacology
Antimicrobial Cationic Peptides/*chemistry
Biofilms/*drug effects
Nitric Oxide Donors/*chemistry
Amino Acid Sequence ; Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Cationic Peptides/pharmacology ; Antimicrobial Cationic Peptides/therapeutic use ; Cephalosporins/pharmacology ; Escherichia coli/physiology ; Hemolysis/drug effects ; Injections, Subcutaneous ; Mice ; Nitric Oxide/metabolism ; Nitric Oxide Donors/pharmacology ; Nitric Oxide Donors/therapeutic use ; Staphylococcal Infections/drug therapy ; Staphylococcal Infections/pathology ; Staphylococcus aureus/physiology
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Substance Nomenclature:
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0 (Anti-Bacterial Agents)
0 (Antimicrobial Cationic Peptides)
0 (Cephalosporins)
0 (Nitric Oxide Donors)
31C4KY9ESH (Nitric Oxide)
3XIY7HJT5L (cephalosporin C)
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Entry Date(s):
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Date Created: 20200814 Date Completed: 20201207 Latest Revision: 20201214
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Update Code:
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20240105
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DOI:
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10.1021/acs.jmedchem.9b01832
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PMID:
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32787095
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Implantable medical device-related infections with biofilms have become a significant challenge in clinics. Based on the potential bacteria biofilm dispersing effect of nitric oxide (NO) and the unique antibacterial activity of antimicrobial peptides (AMP), we synthesized five peptides and selected the most potent one to conjugate its N-terminal with a furoxan moiety to offer a hitherto unknown NO-donating antimicrobial peptide ( FOTyr-AMP ), which exhibited Staphylococcus aureus and Escherichia coli biofilm dispersion and eradication, and potent antibacterial activities in vitro. In an implanted biofilm infection mice model, topical subcutaneous injection of FOTyr-AMP allowed synergetic eradication of bacterial biofilms and potent antibacterial activity, superior to the antibiotic cephalosporin C. Given the low hemolysis effect, little influence on the blood pressure, and potent in vivo efficacy of FOTyr-AMP , it is clear that subcutaneous administration of FOTyr-AMP could be a promising approach for the intervention of medical device-related biofilm infections with desirable safety.
