| Autor: |
Pedro M. Alves, Rúben F. Pereira, Beatriz Costa, Natália Tassi, Cátia Teixeira, Victoria Leiro, Cláudia Monteiro, Paula Gomes, Fabíola Costa, M. Cristina L. Martins |
| Přispěvatelé: |
Instituto de Investigação e Inovação em Saúde |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
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 towards 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 μmol of Dhvar5/g) were achieved, while in NorChit-Ct-Dhvar5 conjugation yield was 30% (55 μmol of Dhvar5/g). Finally, NorChitDhvar5 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 towards the fabrication of antibacterial biomaterials. Work financially supported by Portuguese funds through FCT-MCTES as part of project “AntINFECT“ (POCI-01-0145-FEDER-031781). FCT-MCTES is further acknowledged for funding LAQV-REQUIMTE Research Unit (UIDB/50006/2020). P.A. thanks FCT for the doctoral grant SFRH/BD/145471/2019 financially supported by national (Norte 2020 Framework) and European Union funds (ESF – European Social Fund). F.C. acknowledges the Junior Researcher contract (CEECIND/01921/2017) funded by national funds through FCT, I. P. V.L. acknowledges her contract in the framework of the project PTDC/NAN-MAT/30898/2017 (FCT - Portuguese funds). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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