Synthetic multivalent antifungal peptides effective against fungi.

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 propertie...

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Autores principales:	Rajamani Lakshminarayanan, Shouping Liu, Jianguo Li, Muruganantham Nandhakumar, Thet Tun Aung, Eunice Goh, Jamie Ya Ting Chang, Padhmanaban Saraswathi, Charles Tang, Siti Radiah Binte Safie, Lim Yih Lin, Howard Riezman, Zhou Lei, Chandra S Verma, Roger W Beuerman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ac6c677bc2d44b58f3161d4fd26c57e
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spelling	oai:doaj.org-article:3ac6c677bc2d44b58f3161d4fd26c57e2021-11-18T08:34:12ZSynthetic multivalent antifungal peptides effective against fungi.1932-620310.1371/journal.pone.0087730https://doaj.org/article/3ac6c677bc2d44b58f3161d4fd26c57e2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24498363/?tool=EBIhttps://doaj.org/toc/1932-6203Taking 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.Rajamani LakshminarayananShouping LiuJianguo LiMuruganantham NandhakumarThet Tun AungEunice GohJamie Ya Ting ChangPadhmanaban SaraswathiCharles TangSiti Radiah Binte SafieLim Yih LinHoward RiezmanZhou LeiChandra S VermaRoger W BeuermanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e87730 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rajamani Lakshminarayanan Shouping Liu Jianguo Li Muruganantham Nandhakumar Thet Tun Aung Eunice Goh Jamie Ya Ting Chang Padhmanaban Saraswathi Charles Tang Siti Radiah Binte Safie Lim Yih Lin Howard Riezman Zhou Lei Chandra S Verma Roger W Beuerman Synthetic multivalent antifungal peptides effective against fungi.
description	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.
format	article
author	Rajamani Lakshminarayanan Shouping Liu Jianguo Li Muruganantham Nandhakumar Thet Tun Aung Eunice Goh Jamie Ya Ting Chang Padhmanaban Saraswathi Charles Tang Siti Radiah Binte Safie Lim Yih Lin Howard Riezman Zhou Lei Chandra S Verma Roger W Beuerman
author_facet	Rajamani Lakshminarayanan Shouping Liu Jianguo Li Muruganantham Nandhakumar Thet Tun Aung Eunice Goh Jamie Ya Ting Chang Padhmanaban Saraswathi Charles Tang Siti Radiah Binte Safie Lim Yih Lin Howard Riezman Zhou Lei Chandra S Verma Roger W Beuerman
author_sort	Rajamani Lakshminarayanan
title	Synthetic multivalent antifungal peptides effective against fungi.
title_short	Synthetic multivalent antifungal peptides effective against fungi.
title_full	Synthetic multivalent antifungal peptides effective against fungi.
title_fullStr	Synthetic multivalent antifungal peptides effective against fungi.
title_full_unstemmed	Synthetic multivalent antifungal peptides effective against fungi.
title_sort	synthetic multivalent antifungal peptides effective against fungi.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3ac6c677bc2d44b58f3161d4fd26c57e
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Synthetic multivalent antifungal peptides effective against fungi.

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