Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0087730
DC FieldValue
dc.titleSynthetic multivalent antifungal peptides effective against fungi
dc.contributor.authorLakshminarayanan, R.
dc.contributor.authorLiu, S.
dc.contributor.authorLi, J.
dc.contributor.authorNandhakumar, M.
dc.contributor.authorAung, T.T.
dc.contributor.authorGoh, E.
dc.contributor.authorChang, J.Y.T.
dc.contributor.authorSaraswathi, P.
dc.contributor.authorTang, C.
dc.contributor.authorSafie, S.R.B.
dc.contributor.authorLin, L.Y.
dc.contributor.authorRiezman, H.
dc.contributor.authorLei, Z.
dc.contributor.authorVerma, C.S.
dc.contributor.authorBeuerman, R.W.
dc.date.accessioned2014-10-16T08:44:46Z
dc.date.available2014-10-16T08:44:46Z
dc.date.issued2014-02-03
dc.identifier.citationLakshminarayanan, R., Liu, S., Li, J., Nandhakumar, M., Aung, T.T., Goh, E., Chang, J.Y.T., Saraswathi, P., Tang, C., Safie, S.R.B., Lin, L.Y., Riezman, H., Lei, Z., Verma, C.S., Beuerman, R.W. (2014-02-03). Synthetic multivalent antifungal peptides effective against fungi. PLoS ONE 9 (2) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0087730
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/95182
dc.description.abstractTaking 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. © 2014 Lakshminarayanan et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0087730
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.contributor.departmentCHEMISTRY
dc.description.doi10.1371/journal.pone.0087730
dc.description.sourcetitlePLoS ONE
dc.description.volume9
dc.description.issue2
dc.description.page-
dc.description.codenPOLNC
dc.identifier.isiut000330626900109
dc.published.statePublished
Appears in Collections:Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0087730.pdf3.97 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

17
checked on Nov 15, 2019

WEB OF SCIENCETM
Citations

18
checked on Nov 15, 2019

Page view(s)

129
checked on Nov 9, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.