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dc.creatorSmith, A. Ian
dc.creatorRajapakse, Niwanthi W.
dc.creatorKleifeld, Oded
dc.creatorLomonte, Bruno
dc.creatorSikanyika, Nkumbu L.
dc.creatorSpicer, Alexander J.
dc.creatorHodgson, Wayne C.
dc.creatorConroy, Paul J.
dc.creatorSmall, David H.
dc.creatorKaye, David M.
dc.creatorParkington, Helena C.
dc.creatorWhisstock, James C.
dc.creatorKuruppu, Sanjaya
dc.date.accessioned2018-05-03T15:48:54Z
dc.date.available2018-05-03T15:48:54Z
dc.date.issued2016
dc.identifier.citationhttps://www.nature.com/articles/srep22413es_ES
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10669/74605
dc.description.abstractNeprilysin (NEP) and endothelin converting enzyme-1 (ECE-1) are two enzymes that degrade amyloid beta in the brain. Currently there are no molecules to stimulate the activity of these enzymes. Here we report, the discovery and characterisation of a peptide referred to as K49-P1-20, from the venom of Bothrops asper which directly enhances the activity of both ECE-1 and NEP. This is evidenced by a 2- and 5-fold increase in the Vmax of ECE-1 and NEP respectively. The K49-P1-20 concentration required to achieve 50% of maximal stimulation (AC50) of ECE-1 and NEP was 1.92 ± 0.07 and 1.33 ± 0.12 μM respectively. Using BLITZ biolayer interferometry we have shown that K49-P1-20 interacts directly with each enzyme. Intrinsic fluorescence of the enzymes change in the presence of K49-P1-20 suggesting a change in conformation. ECE-1 mediated reduction in the level of endogenous soluble amyloid beta 42 in cerebrospinal fluid is significantly higher in the presence of K49-P1-20 (31 ± 4% of initial) compared with enzyme alone (11 ± 5% of initial; N = 8, P = 0.005, unpaired t-test). K49-P1-20 could be an excellent research tool to study mechanism(s) of enzyme stimulation, and a potential novel drug lead in the fight against Alzheimer’s disease.es_ES
dc.language.isoen_USes_ES
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.sourceScientific Reports, vol. 6, Article number 22413es_ES
dc.subjectMyotoxines_ES
dc.subjectSynthetic peptidees_ES
dc.subjectBeta-amyloides_ES
dc.subjectAlzheimeres_ES
dc.subjectSnake venomes_ES
dc.titleN-terminal peptide of myotoxin II from Bothrops asper venom enhances the activity of endothelin converting enzyme and neprilysines_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1038/srep22413
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES


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CC0 1.0 Universal
Except where otherwise noted, this item's license is described as CC0 1.0 Universal