dc.creatorBarrera Guisasola, Exequiel Ernesto
dc.creatorAndujar, Sebastian Antonio
dc.creatorHubin, Ellen
dc.creatorBroersen, Kerensa
dc.creatorKraan, Ivonne M.
dc.creatorMendez, Luciana
dc.creatorDelpiccolo, Carina Maria Lujan
dc.creatorMasman, Marcelo Fabricio
dc.creatorRodríguez, Ana M.
dc.creatorEnriz, Ricardo Daniel
dc.date.accessioned2016-10-26T21:22:08Z
dc.date.accessioned2018-11-06T12:34:13Z
dc.date.available2016-10-26T21:22:08Z
dc.date.available2018-11-06T12:34:13Z
dc.date.created2016-10-26T21:22:08Z
dc.date.issued2015-05
dc.identifierBarrera Guisasola, Exequiel Ernesto; Andujar, Sebastian Antonio; Hubin, Ellen; Broersen, Kerensa; Kraan, Ivonne M.; et al.; New mimetic peptides inhibitors of Аb aggregation. Molecular guidance for rational drug design; Elsevier; European Journal of Medicinal Chemistry; 95; 5-2015; 136-152
dc.identifier0009-4374
dc.identifierhttp://hdl.handle.net/11336/7809
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1867925
dc.description.abstractA new series of mimetic peptides possessing a significant Aβ aggregation modulating effect was reported here. These compounds were obtained based on a molecular modelling study which allowed us to perform a structural-based virtual selection. Monitoring Aβ aggregation by thioflavin T fluorescence and transmission electron microscopy revealed that fibril formation was significantly decreased upon prolonged incubation in presence of the active compounds. Dot blot analysis suggested a decrease of soluble oligomers strongly associated with cognitive decline in Alzheimer´s disease. For the molecular dynamics simulations, we used an Aβ42 pentameric model where the compounds were docked using a blind docking technique. To analyze the dynamic behaviour of the complexes, extensive molecular dynamics simulations were carried out in explicit water. We also measured parameters or descriptors that allowed us to quantify the effect of these compounds as potential inhibitors of Aβ aggregation. Thus, significant alterations in the structure of our Aβ42 protofibril model were identified. Among others we observed the destruction of the regular helical twist, the loss of a stabilizing salt bridge and the loss of a stabilizing hydrophobic interaction in the β1 region. Our results may be helpful in the structural identification and understanding of the minimum structural requirements for these molecules and might provide a guide in the design of new aggregation modulating ligands.
dc.languageeng
dc.publisherElsevier
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ejmech.2015.03.042
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523415002093
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectMOLECULAR
dc.subjectMODELLING
dc.subjectMIMETIC
dc.subjectPEPTIDES
dc.subjectAMYLOID
dc.subjectBETA-RPOTEIN
dc.titleNew mimetic peptides inhibitors of Аb aggregation. Molecular guidance for rational drug design
dc.typeArtículos de revistas
dc.typeArtículos de revistas
dc.typeArtículos de revistas


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