A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens
Addressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectur...
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| Veröffentlicht in: | NPG Asia materials 2021, Vol.13 (1), Article 18 |
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| creator | Yuan, Bing Liu, Jiaojiao Deng, Zhixiong Wei, Lin Li, Wenwen Dou, Yujiang Chen, Zhonglan Zhang, Che Xia, Yu Wang, Jing Zhang, Mengling Yang, Kai Ma, Yuqiang Kang, Zhenhui |
| description | Addressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG
12k
–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL
−1
), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.
Integration and design of existing function units into specialized architectures might show combined and even improved performances of the original components. Here we describe a serial of synthetic antibacterial complexes composed of melittin, a natural antimicrobial peptide, and poly(ethylene glycol), a clinical available agent, as building blocks, which show potent and architecture-modulated antibacterial activity against multidrug-resistant pathogens and decreased cytotoxicity. |
| doi_str_mv | 10.1038/s41427-021-00287-y |
| format | Article |
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12k
–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL
−1
), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.
Integration and design of existing function units into specialized architectures might show combined and even improved performances of the original components. Here we describe a serial of synthetic antibacterial complexes composed of melittin, a natural antimicrobial peptide, and poly(ethylene glycol), a clinical available agent, as building blocks, which show potent and architecture-modulated antibacterial activity against multidrug-resistant pathogens and decreased cytotoxicity.</description><identifier>ISSN: 1884-4049</identifier><identifier>EISSN: 1884-4057</identifier><identifier>DOI: 10.1038/s41427-021-00287-y</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>119/118 ; 631/57 ; 639/638/440 ; Antibiotics ; Antimicrobial agents ; Architecture ; Biocompatibility ; Biomaterials ; Chemistry and Materials Science ; Cytotoxicity ; Drug resistance ; Energy Systems ; Lipids ; Materials Science ; Membranes ; Multidrug resistant organisms ; Optical and Electronic Materials ; Pathogens ; Peptides ; Perforating ; Polyethylene glycol ; Structural Materials ; Surface and Interface Science ; Thin Films ; Toxicity</subject><ispartof>NPG Asia materials, 2021, Vol.13 (1), Article 18</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-c0dac3c826e362ac639c99f59d962a1fd74c5201839eaade401c211cac9ce3c73</citedby><cites>FETCH-LOGICAL-c400t-c0dac3c826e362ac639c99f59d962a1fd74c5201839eaade401c211cac9ce3c73</cites><orcidid>0000-0002-2472-5984 ; 0000-0002-5433-3199 ; 0000-0001-6989-5840</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41427-021-00287-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://doi.org/10.1038/s41427-021-00287-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,864,27924,27925,41120,42189,51576</link.rule.ids></links><search><creatorcontrib>Yuan, Bing</creatorcontrib><creatorcontrib>Liu, Jiaojiao</creatorcontrib><creatorcontrib>Deng, Zhixiong</creatorcontrib><creatorcontrib>Wei, Lin</creatorcontrib><creatorcontrib>Li, Wenwen</creatorcontrib><creatorcontrib>Dou, Yujiang</creatorcontrib><creatorcontrib>Chen, Zhonglan</creatorcontrib><creatorcontrib>Zhang, Che</creatorcontrib><creatorcontrib>Xia, Yu</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Zhang, Mengling</creatorcontrib><creatorcontrib>Yang, Kai</creatorcontrib><creatorcontrib>Ma, Yuqiang</creatorcontrib><creatorcontrib>Kang, Zhenhui</creatorcontrib><title>A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens</title><title>NPG Asia materials</title><addtitle>NPG Asia Mater</addtitle><description>Addressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG
12k
–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL
−1
), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.
Integration and design of existing function units into specialized architectures might show combined and even improved performances of the original components. 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Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG
12k
–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL
−1
), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.
Integration and design of existing function units into specialized architectures might show combined and even improved performances of the original components. Here we describe a serial of synthetic antibacterial complexes composed of melittin, a natural antimicrobial peptide, and poly(ethylene glycol), a clinical available agent, as building blocks, which show potent and architecture-modulated antibacterial activity against multidrug-resistant pathogens and decreased cytotoxicity.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><doi>10.1038/s41427-021-00287-y</doi><orcidid>https://orcid.org/0000-0002-2472-5984</orcidid><orcidid>https://orcid.org/0000-0002-5433-3199</orcidid><orcidid>https://orcid.org/0000-0001-6989-5840</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 119/118 631/57 639/638/440 Antibiotics Antimicrobial agents Architecture Biocompatibility Biomaterials Chemistry and Materials Science Cytotoxicity Drug resistance Energy Systems Lipids Materials Science Membranes Multidrug resistant organisms Optical and Electronic Materials Pathogens Peptides Perforating Polyethylene glycol Structural Materials Surface and Interface Science Thin Films Toxicity |
| title | A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens |
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