Orientational Nanoconjugation with Gold Endows Marked Antimicrobial Potential and Drugability of Ultrashort Dipeptides
Antibiotic resistance is a global threat. Antimicrobial peptides (AMPs) are highly desirable to treat multidrug-resistant pathogen infection. However, few AMPs are clinically available, due to high cost, instability, and poor selectivity. Here, ultrashort AMPs (2-3 residues with an N-terminal cysteine) are designed and assembled as gold nanoparticles. Au-S conjugation and ultrashort size restrict nonspecific reactions and peptide orientation, thus concentrating positively charged residues on the surface. The nanostructured assemblies enormously enhance antimicrobial abilities by 1000-6000-fold and stability. One representative (Au-Cys-Arg-NH2, Au_CR) shows selective antibacterial activity against Staphylococcus aureus with 10 nM minimal inhibitory concentration. Au_CR has comparable or better in vivo antimicrobial potency than vancomycin and methicillin, with low propensity to induce resistance, little side effects, and high stability (17.5 h plasma half-life). Au_CR acts by inducing collapse of membrane potential and rupture of the bacterial membrane. The report provides insights for developing AMP-metal nanohybrids, particularly tethering nonspecific reactions and AMP orientation on the metal surface.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Nano letters - 23(2023), 24 vom: 27. Dez., Seite 11874-11883 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Zhiye [VerfasserIn] |
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| Links: |
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| Themen: |
7440-57-5 |
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| Anmerkungen: |
Date Completed 28.12.2023 Date Revised 31.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.nanolett.3c03909 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Antibiotic resistance is a global threat. Antimicrobial peptides (AMPs) are highly desirable to treat multidrug-resistant pathogen infection. However, few AMPs are clinically available, due to high cost, instability, and poor selectivity. Here, ultrashort AMPs (2-3 residues with an N-terminal cysteine) are designed and assembled as gold nanoparticles. Au-S conjugation and ultrashort size restrict nonspecific reactions and peptide orientation, thus concentrating positively charged residues on the surface. The nanostructured assemblies enormously enhance antimicrobial abilities by 1000-6000-fold and stability. One representative (Au-Cys-Arg-NH2, Au_CR) shows selective antibacterial activity against Staphylococcus aureus with 10 nM minimal inhibitory concentration. Au_CR has comparable or better in vivo antimicrobial potency than vancomycin and methicillin, with low propensity to induce resistance, little side effects, and high stability (17.5 h plasma half-life). Au_CR acts by inducing collapse of membrane potential and rupture of the bacterial membrane. The report provides insights for developing AMP-metal nanohybrids, particularly tethering nonspecific reactions and AMP orientation on the metal surface | ||
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| 700 | 1 | |a Chen, Yaoyao |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Jinai |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dengdeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Le |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Mwangi, James |e verfasserin |4 aut | |
| 700 | 1 | |a He, Chenglu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ya |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiangsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Xingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Kamau, Peter Muiruri |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Ren |e verfasserin |4 aut | |
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