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Oligomerization of FVFLM peptides and their ability to inhibit beta amyloid peptide aggregation: consideration as a possible model

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cris.lastimport.scopus2024-02-12T19:54:03Z
dc.abstract.enPreeclampsia, a pregnancy-specific disorder, shares typical pathophysiological features with protein misfolding disorders including Alzheimer’s disease. Characteristic for preeclampsia is the involvement of multiple proteins of which fragments of SERPINA1 and β-amyloid co-aggregate in urine and placenta of preeclamptic women. To explore the biophysical basis of this interaction, we investigated the multidimensional efficacy of the FVFLM sequence in SERPINA1, as a model inhibitory agent of β-amyloid aggregation. After studying the oligomerization of FVFLM peptides using all-atom molecular dynamics simulations with the GROMOS43a1 force field and explicit water, we report that FVFLM can aggregate and its aggregation is spontaneous with a remarkably faster rate than that recorded for KLVFF (aggregation “hot-spot” from β-amyloid). The fast kinetics of FVFLM aggregation was found to be driven primarily by core-like aromatic interactions originating from the anti-parallel orientation of complementarily uncharged strands. The conspicuously stable aggregation mechanism observed for FVFLM peptides is found not to conform to the popular 'dock-lock' scheme. We also found high propensity of FVFLM for KLVFF binding. When present, FVFLM disrupts the β-amyloid aggregation pathway and we propose that FVFLM-like peptides might be used to prevent the assembly of full-length Aβ or other pro-amyloidogenic peptides into amyloid fibrils
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKouza, Maksim
dc.contributor.authorKloczkowski, Andrzej
dc.contributor.authorBanerji, Angana
dc.contributor.authorKoliński, Andrzej
dc.contributor.authorBuhimschi, Irina A.
dc.date.accessioned2024-01-25T15:43:56Z
dc.date.available2024-01-25T15:43:56Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.description.number4
dc.description.volume19
dc.identifier.doi10.1039/C6CP07145G
dc.identifier.issn1463-9076
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/114590
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofPhysical Chemistry Chemical Physics
dc.relation.pages2990-2999
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleOligomerization of FVFLM peptides and their ability to inhibit beta amyloid peptide aggregation: consideration as a possible model
dc.typeJournalArticle
dspace.entity.typePublication