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Secondary Amine Pendant β-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2022 Feb 02; Vol. 144 (4), pp. 1690-1699. Date of Electronic Publication: 2022 Jan 10. - Publication Year :
- 2022
-
Abstract
- Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking β-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial β-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.
- Subjects :
- Animals
Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Antimicrobial Cationic Peptides chemistry
Escherichia coli drug effects
Hemolysis drug effects
Keratitis drug therapy
Keratitis microbiology
Keratitis pathology
Methicillin-Resistant Staphylococcus aureus drug effects
Methicillin-Resistant Staphylococcus aureus isolation & purification
Mice
Microbial Sensitivity Tests
Peptides chemistry
Peptides pharmacology
Polymers chemistry
Staphylococcal Infections microbiology
Wound Infection microbiology
Amines chemistry
Anti-Bacterial Agents therapeutic use
Methicillin-Resistant Staphylococcus aureus pathogenicity
Peptides therapeutic use
Staphylococcal Infections drug therapy
Wound Infection drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 144
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 35007085
- Full Text :
- https://doi.org/10.1021/jacs.1c10659