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Antimicrobial Peptide-Poly(ethylene glycol) Conjugates: Connecting Molecular Architecture, Solution Properties, and
Zixian Cui1, Matthew A Crawford2, Blake A Rumble2
1Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
ACS Polymers Au
|February 19, 2024
Summary
We developed novel polymer-antimicrobial peptide conjugates that overcome limitations of traditional antibiotics. These conjugates show high antimicrobial activity and stability, offering a promising solution for drug-resistant bacterial infections.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Infectious Diseases
Background:
- Antimicrobial peptides (AMPs) show promise against drug-resistant bacteria but face challenges like toxicity and instability.
- Conjugating AMPs to polymers can improve biocompatibility but often reduces antimicrobial efficacy.
Purpose of the Study:
- To investigate how polymer architecture influences the properties and performance of AMP conjugates.
- To develop AMP-PEG conjugates with enhanced antimicrobial activity, stability, and reduced toxicity.
Main Methods:
- Conjugation of a chemokine-derived AMP (stapled Ac-P9) to linear and star-shaped poly(ethylene glycol) (PEG) with varying arm numbers and lengths.
- Characterization of conjugate solution properties (ζ-potential, size, morphology) and performance (antimicrobial activity, hemolysis, protease resistance).
Main Results:
- Conjugates formed nanoscale structures with reduced ζ-potential, indicating polymer shielding of the cationic AMP.
- An 8-arm PEG conjugate with shorter arms (1.25 kDa) showed increased ζ-potential, larger size, and spherical morphology.
- This short 8-arm conjugate exhibited antimicrobial activity comparable to the free AMP and enhanced protease resistance.
- All conjugates demonstrated low cytotoxicity, and nonlinear architectures improved stability without significantly compromising activity.
Conclusions:
- Nonlinear polymer architectures, particularly star-shaped PEG with high AMP density, offer a favorable balance of enhanced stability and potent antimicrobial activity.
- These AMP-polymer conjugates represent a promising strategy for developing effective treatments against resistant bacterial infections with improved safety profiles.
