The influence of the silver bond on the antimicrobial activity of Tenecin 1
| العنوان: | The influence of the silver bond on the antimicrobial activity of Tenecin 1 |
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| المؤلفون: | de Búrca, Eimear Eichstedlund, Hansen, Stine Maagaard |
| المساهمون: | Jelsbak, Lotte, Diness, Frederik |
| بيانات النشر: | Roskilde Universitet, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Tenecin 1, struktur, fremtidig lægemiddel, antimikrobielle peptider, behandling, HPLC, hæmolyse, antibakteriel aktivitet, biofilm, AMP, CD, LC-MS, Tenecin 1 derivater |
| الوصف: | Baggrund: Den tiltagende udvikling af antibiotikaresistens overfor traditionelt anvendt antibiotika er blevet et stigende problem globalt, og grundet dette er nye behandlingsformer i søgelyset. Antimikrobielle peptider kan være en mulig løsning på denne problematik, og optimering af disse peptider er allerede ved at blive undersøgt. Det kan være nødvendigt at tage andre fremgangsmåder i brug for at stabilisere peptidernes strukturer, hvis de skal bruges som fremtidige terapeutiske midler.Formål: Formålet med dette speciale er derfor at undersøge, hvorvidt den antimikrobielle aktivitet af derivater, der er baseret på den alfa-helikale region af Tenecin 1 mod Staphylococcus aureus, vil blive forbedret efter tilsætningen af sølv.Metode: Undersøgelserne er baseret på analyse af nye data fra HPLC, LC-MS, CD, minimum inhiberende koncentration, biofilm-og hæmolyse forsøg.Resultater: CD-spektrene viste forskellige resultater, hvor resultaterne fra peptid AC m. Ag+, 4c+ m. Ag+ og 4c+n+ m. Ag+ viste et stort potentiale i forhold til at adoptere en alfa-helikal struktur. MIC-værdierne for alle peptider uden tilsat Ag+ viste intet antimikrobielt potentiale, hvorimod alle peptider med tilsat Ag+ viste lovende resultater. Derudover viste peptiderne ingen signifikant aktivitet overfor Staphylococcus aureus biofilm, og ligeledes viste de ingen toksicitet mod humane røde blodceller.Konklusion: Flere kriterier skal imødekommes før antimikrobielle peptider kan anvendes som terapeutiske lægemidler. Visse peptider (AC, 4c+ og 4c+n+) undersøgt i denne afhandling udviste potentiale i form af deres strukturelle ændringer efter tilsætning af Ag+, og samtidig havde de en lav MIC-værdi. Det er dog uvist, i hvilket omfang de frie Ag+-ioner har påvirket resultaterne, og derfor er flere dybdegående eksperimenter nødvendige at udføre. Det kan dog konkluderes, at binding af Ag+-ioner forekommer hos andre peptider end AC, og at dette udviser potentiale i forhold til udvikling af fremtidige lægemidler. Derudover kan det konkluderes, at der er potentiale for peptiderne med ekstra ladninger (4c+ og 4c+n+).Nøgleord: AMP, antibakteriel aktivitet, antimikrobielle peptider, behandling, biofilm, CD, fremtidig lægemiddel, HPLC, hæmolyse, LC-MS, MIC, struktur, Tenecin 1, Tenecin 1 derivater. Background: The rapid development of antibiotic resistance towards traditionally used antibiotics has become an increasing problem globally and therefore novel treatment options are currently in the spotlight. Antimicrobial peptides could be a possible solution to this problem, and the optimisation of these peptides is already being investigated. However, other methods may be needed to stabilise their structures before they can be used as therapeutics.Objective: The objective of this thesis is to investigate whether the antimicrobial activity of the derivatives based on the alpha-helical region within Tenecin 1 against Staphylococcus aureus will improve following the addition of silver.Method: The investigation is based on the analysis of newly provided data from HPLC, LC-MS, CD, minimum inhibitory concentration, biofilm, and haemolysis assays.Results: The CD-spectra showed a variation of results. Based on the CD results, peptide AC w. Ag+, 4c+ w. Ag+ and 4c+n+ w. Ag+ showed great potential in terms of adopting an alpha-helical structure. The MIC-values for all peptides without Ag+ showed no antimicrobial potential, whilst all peptides with Ag+ added showed promising results. The peptides showed no significant activity against Staphylococcus aureus biofilms, and likewise, they did not show toxicity towards human red blood cells.Conclusion: Several criteria must be met before the peptides can be used as therapeutic drugs. Certain peptides (AC, 4c+ and 4c+n+) investigated in this thesis exhibit potential in terms of their structural changes following the addition of Ag+, and likewise, they had a low MIC-value. However, it is unbeknown to which extent free Ag+-ions have affected the results, and therefore more in-depth experiments are necessary. However, it can be concluded that binding of Ag+-ions occurs for other peptides besides AC, and that this exhibits potential, especially for the peptides with additional charges (4c+ and 4c+n+).Key words: AMP, antibacterial activity, antimicrobial peptide, biofilm, CD, haemolysis, HPLC, LC- MS, MIC, potential drug, structure, Tenecin 1, Tenecin 1 derivatives, treatment. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=od_______278::fca3c8b9afd7efe311b7d916971ec91e https://rucforsk.ruc.dk/ws/files/95755120/Speciale__22_maj_.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.od.......278..fca3c8b9afd7efe311b7d916971ec91e |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |