Bioavailability and biocompatibility of tetrabranched antifungal peptides.

Abstract

Fungal keratitis is the second leading cause of corneal blindness in the developing countries. Fungal resistance becomes a serious threat in maintaining public health due to the recurrent use of antibiotic therapy. Thus, new therapeutic approach is essential to replace the conventional antibiotics. B4010, a tetrabranched antifungal peptide is developed by Prof. Roger Beuerman’s group at SERI. The aim of this study is to assess the therapeutic potential of B4010 and its four truncated analogues and the scrambled peptide for topical and systemic fungal infections. The antifungal properties of these peptides were tested against 3 C. albicans and their antifungal activities were determined in presence of trypsin (1:100 enzyme: substrate ratio), 25% human serum and 50% tear fluid in vitro. Furthermore, we determined the dissipation of cytoplasmic membrane potential upon adding various peptides to C. albicans ATCC 10231 as well as the haemolytic activity of the peptides in rabbit blood. B4010∆1-5 has evidently shown to be the most effective peptide with low MIC of 12uM and considerably stable in the presence of trypsin, human serum and tear fluid, and exhibit good fungicidal action but strong haemolytic activity. This concludes B4010∆1-5 is the ideal B4010 truncated derivative for further drug-optimization process.