Synthesis and Antibiotic Activity of Chitosan-Based Comb-like Co-Polypeptides

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Microbiology

Background:

• Multidrug-resistant Gram-negative bacterial infections pose a significant global health threat.
• Antimicrobial Peptides (AMPs) are potent, broad-spectrum agents effective against resistant organisms but have limitations in selectivity and efficacy.
• Developing synthetic AMP analogs with improved properties is crucial for combating antimicrobial resistance.

Purpose of the Study:

• To design and synthesize novel antimicrobial agents that mimic AMPs' mode of action.
• To explore chitosan-graft-polypeptide structures as potential drug candidates.
• To evaluate the efficacy of these novel polymers against clinically significant pathogens and biofilms.

Main Methods:

• Synthesis of graft copolymers using chitosan backbone and AMP side chains via ring-opening polymerization of N-carboxyanhydride of l-lysine and l-leucine.
• Investigation of both random and block copolymer side chain architectures.
• Assessment of antimicrobial activity against relevant bacterial strains and biofilm disruption assays.

Main Results:

• The synthesized chitosan-graft-polypeptide copolymers demonstrated significant antimicrobial activity.
• These novel polymers effectively disrupted the formation of bacterial biofilms.
• Both random and block copolymer structures showed potential as antimicrobial agents.

Conclusions:

• Chitosan-graft-polypeptide structures represent a promising new class of antimicrobial agents.
• These biomimetic polymers offer a potential strategy to overcome limitations of natural AMPs.
• The developed graft copolymers hold significant potential for biomedical applications in combating infectious diseases.