In response to the global rise in antibiotic-resistant bacteria 1, significant research efforts are being devoted to developing new effective antibacterial drugs. This study draws inspiration from natural antimicrobial peptides (AMPs), that are macromolecules able to selectively disrupt bacterial membranes, due to their amphiphilic nature 2. Key features of these systems, are the presence of cationic and hydrophobic groups in their structure.
We synthesized a library of well-defined amphiphilic random and block copolymers using bio-based acrylates, respectively containing amino acids with various side chains (Ala, Phe, Lys) as the cationic components, and tetrahydrogeraniol (THG) as the hydrophobic component, employing controlled Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization 3. The antimicrobial activity and cytotoxicity of these copolymers were evaluated against E. coli, S. aureus, and mouse fibroblasts (L929). Both random and block copolymers displayed antimicrobial activity influenced by the cationic/hydrophobic balance, yet block copolymers provided greater control and improved selectivity, particularly in Lys-based variants that achieved potent activity against E. coli and moderate efficacy against S. aureus. Random copolymers typically required higher cationic content for comparable antimicrobial activity, risking elevated cytotoxicity. In contrast, block copolymers—especially those with an equimolar ratio of cationic and hydrophobic segments—offered superior antimicrobial performance and lower toxicity, highlighting their potential for more targeted and biocompatible applications. Live/dead staining and SEM imaging confirmed that its antimicrobial effect was achieved through disruption of the bacterial cell membrane integrity.
1) Kumar, M.; Sarma, D. K.; Shubham, S.; Kumawat, M.; Verma, V.; Nina, P. B.; Jp, D.; Kumar, S.; Singh, B.; Tiwari, R. R. Futuristic Non-antibiotic Therapies to Combat Antibiotic Resistance: A Review. Front Microbiol 2021, 12, 609459. DOI: 10.3389/fmicb.2021.609459.
(2) Boparai, J. K.; Sharma, P. K. Mini review on antimicrobial peptides, sources, mechanism and recent applications. Protein and peptide letters 2020, 27 (1), 4-16. DOI: 10.2174/0929866526666190822165812.
(3) Hatton, F. L. Recent advances in RAFT polymerization of monomers derived from renewable resources. Polymer Chemistry 2020, 11 (2), 220-229. DOI: 10.1039/c9py01128e.