title: Conjugation of Polyphosphoester and Antimicrobial Peptide for Enhanced Bactericidal Activity and Biocompatibility.
abstract: Enhancing the bactericidal activity and moderating the toxicity are two important challenges in the design of upcoming antimicrobial compounds. Herein, antimicrobial macromolecules were developed by conjugating CysHHC10 peptide and polyphosphoester for the modulation of microbiocidal activity and biocompatibility. The conjugation was carried out via thiol-yne "click" chemistry between the cysteine terminal of the peptide and the pendant propargyl moieties of the polyphosphoester. The bactericidal efficacy of the polyphosphoester-peptide conjugates were investigated by microbial growth inhibition toward the Gram-positive and Gram-negative bacteria. On the basis of peptide mass fraction, the polyphosphoester-peptide conjugates exhibited lower values of minimum inhibitory concentration than that of the free peptide. The polyphosphoester-peptide conjugates also exhibited ultralow hemolytic characteristic at a concentration of 4000 μg/mL, indicating significant improvement of erythrocytes compatibility as compared to the free peptide that readily caused lysis of 50% of red blood cells at 1000 μg/mL. Cytotoxicity of the polyphosphoester-peptide conjugates toward 3T3 fibroblast cells was also reduced in comparison to that of the free peptide. Conjugation of the polyphosphoester thus improves the bactericidal efficacy and biocompatibility of the antimicrobial peptide.
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , Kent Ridge, Singapore 119260.
authors.forename: Dicky
authors.initials: D
authors.lastname: Pranantyo
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , Kent Ridge, Singapore 119260.
authors.forename: Li Qun
authors.initials: LQ
authors.lastname: Xu
authors.affiliation: Department of Chemical and Biomolecular Engineering, National University of Singapore , Kent Ridge, Singapore 119260.
authors.forename: En-Tang
authors.initials: ET
authors.lastname: Kang
authors.affiliation: Centre for Antimicrobial Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University , Singapore 637459.
authors.forename: Mya Khin
authors.initials: MK
authors.lastname: Mya
authors.affiliation: Centre for Antimicrobial Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University , Singapore 637459.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Chan-Park
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects*; D004952:Esters / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D004952:Esters; D011108:Polymers; D011122:Polyphosphates