Characterisation and formulation of natural cyclodecapeptides with anti-Candida activity
| dc.contributor.advisor | Rautenbach, Marina | en_ZA |
| dc.contributor.author | Masoudi, Yasamin | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Science. Dept. of Biochemistry. | en_ZA |
| dc.date.accessioned | 2021-03-04T12:41:59Z | |
| dc.date.accessioned | 2021-04-21T14:32:40Z | |
| dc.date.available | 2021-03-04T12:41:59Z | |
| dc.date.available | 2021-04-21T14:32:40Z | |
| dc.date.issued | 2021-03 | |
| dc.description | Thesis (MSc)--Stellenbosch University, 2021. | en_ZA |
| dc.description.abstract | ENGLISH ABSTRACT: The increase in the number of fungal infections since the 1980s is a major concern globally. Fungal infections affect various medical and agricultural sectors. A limited number of available antifungal drugs in addition to the development of the antifungal drug resistance, urge the need for the development of new antifungal drugs. Candida albicans and Candida glabrata are the two most common causes of topical and systemic Candida infections, and specifically prone to drug resistance. Therefore, the next generation of antifungal drugs has to be compounds with a low probability to elicit resistance. The tyrocidines (Trcs) and analogues are cyclic decapeptides with a broad antimicrobial spectrum and proven anti-Candida activity. The development of resistance is less likely due to their rapid mode of action and multiple targets. The Trcs and analogues have agreat tendency to oligomerise and the antimicrobial activity of the Trcs may be dependent on their ability to form active oligomers. In this study, we aimed to manipulate the Trc oligomerisation by combining it with cellulose derivatives as formulants. The goal was to increase the anti-Candida activity as well as the stability of theses peptides in solution. Furthermore, if a concomitant decrease in the toxicity against human erythrocytes would alsobe beneficial. The oligomerisation profile of Trcs is driven by four main factors, namely, concentration, maturation time, peptide structure and the viscosity of the cellulose derivatives used in the formulation. The oligomerisation of Trcs is a dynamic arrangement and rearrangement of the peptide in the Trc mixture throughout the maturation period. For the more viscous cellulose-type formulants, this rearrangement resulted in the release of the more dimeric oligomers and increased the anti-Candida activity of the Trc mixture, However, for pure peptides such as TrcA and TpcC, both formulation and the maturationtime did not alter the anti-Candida activity. This could be that TrcA oligomers are highly stable and maturation time does not result in releasing of more active moieties. Tic is inherently less active, and it may not have the optimal structure to interact with the Candida target. It was observed that a high concentration of cellulose derivatives significantly increased the anti-Candida activity of the Tic mixture, as well as stabilising the tic peptides in solutions, as detected with fluorescence. Unfortunately, none of the cellulose formulations of try mix decreased the haemolytic activity against human erythrocytes. However, anti-Candida activity was maintained and/or improved, as the solution stability of the peptides in the Trc mixture was improved. | en_ZA |
| dc.description.version | Masters | en_ZA |
| dc.format.extent | xii, (128 pages) : illustrations (some color) | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/109933 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | Candida | en_ZA |
| dc.subject | Fungal infections | en_ZA |
| dc.subject | Tyrocidines | en_ZA |
| dc.subject | Antimicrobial activity | en_ZA |
| dc.subject | Peptides -- Chemistry | en_ZA |
| dc.subject | Antifungal drug resistance | en_ZA |
| dc.subject | UCTD | en_ZA |
| dc.title | Characterisation and formulation of natural cyclodecapeptides with anti-Candida activity | en_ZA |
| dc.type | Thesis | en_ZA |