Effect of truncation on antifungal properties of tetrabranched peptides.
Ocular fungal infections are worldwide health concern, resulting in a need to develop new drugs with greater effectiveness. B4010, a tetrabranched antifungal peptide that permeabilizes cytoplasmic membranes, was developed in Prof. Roger Beuerman’s lab. The aims of this project were to determine the...
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| Format: | Final Year Project (FYP) |
| Language: | English |
| Published: |
2012
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| Online Access: | http://hdl.handle.net/10356/50859 |
| Summary: | Ocular fungal infections are worldwide health concern, resulting in a need to develop new drugs with greater effectiveness. B4010, a tetrabranched antifungal peptide that permeabilizes cytoplasmic membranes, was developed in Prof. Roger Beuerman’s lab. The aims of this project were to determine the effect of structural truncation on the antifungal properties of B4010 tested against five Candida albicans strains and evaluate their therapeutic potential for topical and systemic fungal infections. The effects of truncation were tested with minimum inhibitory concentration (MIC) and membrane permeability via SYTOX green assay. The therapeutic potential was determined via cell viability in 50% tear fluid and MIC in 5% sera. B4010 and its analogues (except B4010∆1-4) showed strong antifungal properties against all five strains. Further analysis demonstrated that the number of amino acids in the repeats contributes to antifungal potency. To maintain optimum antifungal properties, a minimum net charge of +20 and hydrophobicity of -2.1 kcal/mol is required. However, serum stability and candidacidal activity in tear fluid results suggested that shorter copy lengths may be better than longer analogues. This study has presented an optimization profile of B4010 and its analogues that would enable the development of a new class of therapeutically important antifungal compounds. |
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