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|Title:||Synthetic multivalent antifungal peptides effective against fungi||Authors:||Lakshminarayanan, Rajamani
Aung, Thet Tun
Chang, Jamie Ya Ting
Safie, Siti Radiah Binte
Lin, Lim Yih
Verma, Chandra S.
Beuerman, Roger W.
|Keywords:||DRNTU::Science::Biological sciences::Biochemistry||Issue Date:||2014||Source:||Lakshminarayanan, R., Liu, S., Li, J., Nandhakumar, M., Aung, T. T., Goh, E., et al. (2014). Synthetic multivalent antifungal peptides effective against fungi. PLoS ONE, 9(2), e87730-.||Series/Report no.:||PLoS ONE||Abstract:||Taking advantage of the cluster effect observed in multivalent peptides, this work describes antifungal activity and possible mechanism of action of tetravalent peptide (B4010) which carries 4 copies of the sequence RGRKVVRR through a branched lysine core. B4010 displayed better antifungal properties than natamycin and amphotericin B. The peptide retained significant activity in the presence of monovalent/divalent cations, trypsin and serum and tear fluid. Moreover, B4010 is non-haemolytic and non-toxic to mice by intraperitoneal (200 mg/kg) or intravenous (100 mg/kg) routes. S. cerevisiae mutant strains with altered membrane sterol structures and composition showed hyper senstivity to B4010. The peptide had no affinity for cell wall polysaccharides and caused rapid dissipation of membrane potential and release of vital ions and ATP when treated with C. albicans. We demonstrate that additives which alter the membrane potential or membrane rigidity protect C. albicans from B4010-induced lethality. Calcein release assay and molecular dynamics simulations showed that the peptide preferentially binds to mixed bilayer containing ergosterol over phophotidylcholine-cholesterol bilayers. The studies further suggested that the first arginine is important for mediating peptide-bilayer interactions. Replacing the first arginine led to a 2–4 fold decrease in antifungal activities and reduced membrane disruption properties. The combined in silico and in vitro approach should facilitate rational design of new tetravalent antifungal peptides.||URI:||https://hdl.handle.net/10356/102430
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0087730||Rights:||© 2014 Lakshminarayanan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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