# Tuning the Structure–Functional Properties Within Peptide-Mimicking Antimicrobial Hydrogels

**Authors:** Samuel T. Attard, Vina R. Aldilla, Rajesh Kuppusamy, Renxun Chen, David StC Black, Pall Thordarson, Mark D. P. Willcox, Naresh Kumar

PMC · DOI: 10.3390/antibiotics14111118 · 2025-11-05

## TL;DR

This study explores how structural changes in antimicrobial hydrogels affect their physical and antimicrobial properties, offering a guide for optimizing their design.

## Contribution

The paper identifies structural features that influence hydrogelation and antimicrobial activity in peptide-mimicking hydrogels.

## Key findings

- Eleven novel anthranilamide compounds were synthesized, with three forming hydrogels.
- Altering aromatic caps and amino acid side chains tunes mechanical strength and fiber morphology.
- Certain structural features were found to reduce hydrogelation strength and stiffness.

## Abstract

Background/Objectives: There is a growing demand for the development of novel antimicrobial agents due to their efficacy being eroded by increasing antimicrobial resistance. Antimicrobial hydrogels have been reported as a method to treat bacterial infections. Methods: This study explores how different structural features are important for the hydrogelation properties of amphiphilic antimicrobial peptide-mimics through rheology and AFM, as well as properties important for antimicrobial activity measured through MIC. Results: Eleven novel peptide-mimicking anthranilamides containing various structural features were synthesised in 4–7 steps. Of these peptide-mimics, three novel compounds formed hydrogels, and it was identified that their mechanical strength, secondary structure, and fibre morphology could be tuned by altering the aromatic cap or the amino acid side chain. In conjunction, several structural features were identified that reduce hydrogelation strength and stiffness. Conclusions: This work provides an insight into how the structural features of low-molecular-weight self-assembling hydrogels can translate to differing physical and potent antimicrobial properties. This work provides a rational guide to optimising physical hydrogel properties, as well as highlighting features that may reduce hydrogelation.

## Full-text entities

- **Diseases:** bacterial infections (MESH:D001424)
- **Chemicals:** anthranilamides (MESH:C000219)

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12649725/full.md

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Source: https://tomesphere.com/paper/PMC12649725