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

Detalhes bibliográficos
Autor(a) principal: Alves, PM
Data de Publicação: 2022
Outros Autores: Pereira, RF, Costa, B, Tassi, N, Teixeira, C, Leiro, V, Monteiro, C, Gomes, P, Costa, F, Martins, MCL
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/142702
Resumo: 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.
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spelling Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial BiomaterialsPeptidopolysaccharidesSurface modificationCovalent conjugationThiol-enePeptide tetheringDhvar5Covalent 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.American Chemical Society2022-06-302022-06-30T00:00:00Z2023-06-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10216/142702eng2637-610510.1021/acsapm.2c00563Alves, PMPereira, RFCosta, BTassi, NTeixeira, CLeiro, VMonteiro, CGomes, PCosta, FMartins, MCLinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T13:57:49Zoai:repositorio-aberto.up.pt:10216/142702Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:51:02.718481Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
title Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
spellingShingle Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
Alves, PM
Peptidopolysaccharides
Surface modification
Covalent conjugation
Thiol-ene
Peptide tethering
Dhvar5
title_short Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
title_full Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
title_fullStr Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
title_full_unstemmed Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
title_sort Thiol-Norbornene Photoclick Chemistry for Grafting Antimicrobial Peptides onto Chitosan to Create Antibacterial Biomaterials
author Alves, PM
author_facet Alves, PM
Pereira, RF
Costa, B
Tassi, N
Teixeira, C
Leiro, V
Monteiro, C
Gomes, P
Costa, F
Martins, MCL
author_role author
author2 Pereira, RF
Costa, B
Tassi, N
Teixeira, C
Leiro, V
Monteiro, C
Gomes, P
Costa, F
Martins, MCL
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Alves, PM
Pereira, RF
Costa, B
Tassi, N
Teixeira, C
Leiro, V
Monteiro, C
Gomes, P
Costa, F
Martins, MCL
dc.subject.por.fl_str_mv Peptidopolysaccharides
Surface modification
Covalent conjugation
Thiol-ene
Peptide tethering
Dhvar5
topic Peptidopolysaccharides
Surface modification
Covalent conjugation
Thiol-ene
Peptide tethering
Dhvar5
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-30
2022-06-30T00:00:00Z
2023-06-30T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/142702
url https://hdl.handle.net/10216/142702
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2637-6105
10.1021/acsapm.2c00563
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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