Short, Lipidated Dendrimeric γ-AApeptides as New Antimicrobial Peptidomimetics

Antibiotic resistance is one of the most significant issues encountered in global health. There is an urgent demand for the development of a new generation of antibiotic agents combating the emergence of drug resistance. In this article, we reported the design of lipidated dendrimeric γ-AApeptides a...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-03, Vol.24 (7), p.6407
Main Authors: Wang, Yafeng, Xue, Menglin, Gao, Ruixuan, Chakraborty, Soumyadeep, Wang, Shaohui, Zhao, Xue, Gu, Meng, Cao, Chuanhai, Sun, Xingmin, Cai, Jianfeng
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents - pharmacology
Antibacterial agents
Antibiotic resistance
Antibiotics
Antimicrobial agents
Bacteria
Bacterial infections
broad spectrum activity
Communication
dendrimeric γ-AApeptides
Dendrimers
Drug development
Drug resistance
Drug resistance in microorganisms
E coli
Experiments
Gram-negative bacteria
Gram-positive bacteria
Lipids
Membranes
Methicillin
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Microscopy
NMR
Nuclear magnetic resonance
Peptides
Peptidomimetics
Peptidomimetics - pharmacology
Permeability
Public health
Staphylococcus aureus
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Summary:Antibiotic resistance is one of the most significant issues encountered in global health. There is an urgent demand for the development of a new generation of antibiotic agents combating the emergence of drug resistance. In this article, we reported the design of lipidated dendrimeric γ-AApeptides as a new class of antimicrobial agents. These AApeptides showed excellent potency and broad-spectrum activity against both Gram-positive bacteria and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The mechanistic studies revealed that the dendrimeric AApeptides could kill bacteria rapidly through the permeabilization of bacterial membranes, analogous to host-defense peptides (HDPs). These dendrimers also did not induce antibiotic resistance readily. The easy access to the synthesis, together with their potent and broad-spectrum activity, make these lipidated dendrimeric γ-AApeptides a new generation of antibacterial agents.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24076407