Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials

Covalent conjugation of antimicrobial peptides (AMP) is considered an effective approach to overcome their potential degradation in vivo. As the high cost of AMP-based therapies is one of the major hurdles toward their clinical application, it is urgently needed to explore high yield reactions. Herein, the highly efficient thiol-norbornene photoclick chemistry (TNPC) was explored for AMP grafting onto chitosan. Norbornenes were introduced onto chitosan (NorChit) in an aqueous/organic system, followed by UV-triggered conjugation of N- and C-terminus cysteine-modified Dhvar5 (NorChit-Dhvar5). Up to 0.38 norbornene groups per chitosan repeating unit and up to 43% conjugation yield in NorChit-Nt-Dhvar5 (80 mu mol of Dhvar5/g) were achieved, while in NorChit-Ct-Dhvar5 conjugation yield was 30% (55 mu mol of Dhvar5/g). Finally, NorChit-Dhvar5 ultrathin films showed up to a 35% reduction of total adhered Gram-positive Staphylococcus epidermidis and increased the adhesion and killing of Gram-negative Pseudomonas aeruginosa compared to unmodified chitosan. Moreover, NorChit-Dhvar5 was noncytotoxic to human neonatal dermal fibroblasts, according to ISO 10993-1. Overall, our findings indicate TNPC as a high yield strategy for AMP grafting onto norbornene-functionalized biopolymers toward the fabrication of antibacterial biomaterials.

Automated summary

In this study, a highly efficient reaction method, TNPC, was explored for grafting AMP onto chitosan, resulting in the fabrication of antibacterial biomaterials with high conjugation yield.