| 1. |
- Berglin, Mattias, 1970, et al.
(författare)
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Flexible and Biocompatible Antifouling Polyurethane Surfaces Incorporating Tethered Antimicrobial Peptides through Click Reactions
- 2024
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Ingår i: Macromolecular Bioscience. - : John Wiley and Sons Inc. - 1616-5187 .- 1616-5195. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- Efficient, simple antibacterial materials to combat implant-associated infections are much in demand. Herein, the development of polyurethanes, both cross-linked thermoset and flexible and versatile thermoplastic, suitable for “click on demand” attachment of antibacterial compounds enabled via incorporation of an alkyne-containing diol monomer in the polymer backbone, is described. By employing different polyolic polytetrahydrofurans, isocyanates, and chain extenders, a robust and flexible material comparable to commercial thermoplastic polyurethane is prepared. A series of short synthetic antimicrobial peptides are designed, synthesized, and covalently attached in a single coupling step to generate a homogenous coating. The lead material is shown to be biocompatible and does not display any toxicity against either mouse fibroblasts or reconstructed human epidermis according to ISO and OECD guidelines. The repelling performance of the peptide-coated materials is illustrated against colonization and biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis on coated plastic films and finally, on coated commercial central venous catheters employing LIVE/DEAD staining, confocal laser scanning microscopy, and bacterial counts. This study presents the successful development of a versatile and scalable polyurethane with the potential for use in the medical field to reduce the impact of bacterial biofilms.
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| 2. |
- Hansson, Adam, 1993, et al.
(författare)
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Preventing E. coli Biofilm Formation with Antimicrobial Peptide-Functionalized Surface Coatings: Recognizing the Dependence on the Bacterial Binding Mode Using Live-Cell Microscopy
- 2024
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Ingår i: ACS APPLIED MATERIALS & INTERFACES. - : American Chemical Society. - 1944-8244 .- 1944-8252. ; 16:6, s. 6799-6812
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) can kill bacteria by destabilizing their membranes, yet translating these molecules' properties into a covalently attached antibacterial coating is challenging. Rational design efforts are obstructed by the fact that standard microbiology methods are ill-designed for the evaluation of coatings, disclosing few details about why grafted AMPs function or do not function. It is particularly difficult to distinguish the influence of the AMP's molecular structure from other factors controlling the total exposure, including which type of bonds are formed between bacteria and the coating and how persistent these contacts are. Here, we combine label-free live-cell microscopy, microfluidics, and automated image analysis to study the response of surface-bound Escherichia coli challenged by the same small AMP either in solution or grafted to the surface through click chemistry. Initially after binding, the grafted AMPs inhibited bacterial growth more efficiently than did AMPs in solution. Yet, after 1 h, E. coli on the coated surfaces increased their expression of type-1 fimbriae, leading to a change in their binding mode, which diminished the coating's impact. The wealth of information obtained from continuously monitoring the growth, shape, and movements of single bacterial cells allowed us to elucidate and quantify the different factors determining the antibacterial efficacy of the grafted AMPs. We expect this approach to aid the design of elaborate antibacterial material coatings working by specific and selective actions, not limited to contact-killing. This technology is needed to support health care and food production in the postantibiotic era.
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| 3. |
- Karlsen, Eskil, et al.
(författare)
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Anti-colonization effect of au surfaces with self-assembled molecular monolayers functionalized with antimicrobial peptides on s. Epidermidis
- 2021
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Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- Medical devices with an effective anti-colonization surface are important tools for com-batting healthcare-associated infections. Here, we investigated the anti-colonization efficacy of antimicrobial peptides covalently attached to a gold model surface. The gold surface was modified by a self-assembled polyethylene glycol monolayer with an acetylene terminus. The peptides were covalently connected to the surface through a copper-catalyzed [3 + 2] azide-acetylene coupling (CuAAC). The anti-colonization efficacy of the surfaces varied as a function of the antimicrobial activity of the peptides, and very effective surfaces could be prepared with a 6 log unit reduction in bacterial colonization. © 2021 by the authors.
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| 4. |
- Rothweiler, Ulli, et al.
(författare)
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Luciferin and derivatives as a DYRK selective scaffold for the design of protein kinase inhibitors
- 2015
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier. - 0223-5234 .- 1768-3254. ; 94, s. 140-148
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Tidskriftsartikel (refereegranskat)abstract
- D-Luciferin is widely used as a substrate in luciferase catalysed bioluminescence assays for in vitro studies. However, little is known about cross reactivity and potential interference of D-luciferin with other enzymes. We serendipitously found that firefly luciferin inhibited the CDK2/Cyclin A protein kinase. Inhibition profiling of D-luciferin over a 103-protein kinase panel showed significant inhibition of a small set of protein kinases, in particular the DYRK-family, but also other members of the CMGC-group, including ERK8 and CK2. Inhibition profiling on a 16-member focused library derived from D-luciferin confirms that D-luciferin represents a DYRK-selective chemotype of fragment-like molecular weight. Thus, observation of its inhibitory activity and the initial SAR information reported here promise to be useful for further design of protein kinase inhibitors with related scaffolds.
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| 5. |
- Stensen, Wenche, et al.
(författare)
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Short cationic antimicrobial peptides display superior antifungal activities toward Candidiasis and Onychomycosis in comparison with Terbinafine and Amorolfine
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:10, s. 3595-3600
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Tidskriftsartikel (refereegranskat)abstract
- Novel antifungals are in high demand due to the challenges associated with resistant, persistent, and systemic fungal infections. Synthetic mimics of antimicrobial peptides are emerging as a promising class of compounds for antifungal treatment. In the current study, five synthetic cationic antimicrobial tripeptides were evaluated as antifungal therapeutics against 24 pathogenic strains of fungi. Three of the peptides displayed strong general antifungal properties at low micromolar inhibitory concentrations. The most promising peptide, compound 5, was selected and evaluated as an antifungal remedy for Candida albicans candidiasis in a human skin model and for the treatment of Trichophyton rubrum induced onychomycosis in an infected human nail model. Compound 5 was shown to display antifungal properties and a rapid mode of action superior to those of both the commercial comparators Loceryl and Lamisil. Compound 5 was also active against a clinical isolate of Candida albicans with acquired fluconazole resistance.
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| 6. |
- Trepos, Rozenn, et al.
(författare)
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Antifouling compounds from the Sub-Arctic ascidian Synoicum pulmonaria: Synoxazolidinones A and C, Pulmonarins A and B, and synthetic analogues.
- 2014
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Ingår i: Journal of natural products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 77:9, s. 2105-2113
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Tidskriftsartikel (refereegranskat)abstract
- The current study describes the antifouling properties of four members belonging to the recently discovered synoxazolidinone and pulmonarin families, isolated from the sub-Arctic sessile ascidian Synoicum pulmonaria collected off the Norwegian coast. Four simplified synthetic analogues were also prepared and included in the study. Several of the studied compounds displayed MIC values in the micro-nanomolar range against 16 relevant marine species involved in both the micro- and macrofouling process. Settlement studies on Balanus improvisus cyprids indicated a deterrent effect and a low toxicity for selected compounds. The two synoxazolidinones displayed broad activity and are shown to be among the most active natural antifouling bromotyrosine derivatives described. Synoxazolidinone C displayed selected antifouling properties comparable to the commercial antifouling product Sea-Nine-211. The pulmonarins prevented the growth of several bacterial strains at nanomolar concentrations but displayed a lower activity toward microalgae and no effect on barnacles. The linear and cyclic synthetic peptidic mimics also displayed potent antifouling activities mainly directed against bacterial adhesion and growth.
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