title: Tethering antimicrobial peptides onto chitosan: Optimization of azide-alkyne "click" reaction conditions.
abstract: Antimicrobial peptides (AMP) are promising alternatives to classical antibiotics, due to their high specificity and potency at low concentrations, and low propensity to elicit pathogen resistance. Immobilization of AMP onto biomaterials is an emergent field of research, towards creation of novel antimicrobial materials able to avoid formation of biofilms on the surfaces of medical devices. Herein, we report the chemical route towards one such material, where chitosan was used as biocompatible carrier for the covalent grafting of Dhvar-5, a well-known potent AMP, via the chemoselective ("click") Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The material's structure, as well as peptide loading, were confirmed by Fourier-transformed infra-red (FT-IR) and X-ray photoelectron (XPS) spectroscopies, and by Amino Acid Analysis (AAA), respectively. Results herein reported demonstrate that, with proper optimization, the "click" CuAAC is an attractive approach for the tethering of AMP onto chitosan, in order to create novel antimicrobial materials potentially valuable for biomedical applications.
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal; i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Barbosa
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
authors.forename: Fabíola M T A
authors.initials: FM
authors.lastname: Costa
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: M Cristina L
authors.initials: MC
authors.lastname: Martins
authors.affiliation: UCIBIO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal. Electronic address: pgomes@fc.up.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Gomes
mesh_terms: D000480:Alkynes; D000890:Anti-Infective Agents / Q000737:chemistry*; D001386:Azides; D048271:Chitosan / Q000737:chemistry*; D057930:Click Chemistry; D010455:Peptides / Q000737:chemistry*; D056951:Photoelectron Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000480:Alkynes; D000890:Anti-Infective Agents; D001386:Azides; D010455:Peptides; D048271:Chitosan
keywords: Aminoguanidine hydrochloride (PubChem CID: 2734687); Antibiotics; Antimicrobial peptides; Azide-alkyne coupling; Biofilms; Chitosan; Click chemistry; CuAAC; Imidazole-1-sulfonyl azide hydrochloride (PubChem CID: 23583982); Propargylamine (PubChem CID: 239041); Tris(3-hydroxypropyltriazolylmethyl)amine (PubChem CID: 85325313)