Sequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicity

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dc.citation.volume233
dc.contributor.authorSilva, Emerson R. [UNIFESP]
dc.contributor.authorListik, Eduardo
dc.contributor.authorHan, Sang W. [UNIFESP]
dc.contributor.authorAlves, Wendel A.
dc.contributor.authorSoares, Bruna M.
dc.contributor.authorReza, Mehedi
dc.contributor.authorRuokolainen, Janne
dc.contributor.authorHamley, Ian W.
dc.coverageAmsterdam
dc.date.accessioned2020-07-08T13:09:47Z
dc.date.available2020-07-08T13:09:47Z
dc.date.issued2018
dc.description.abstractWe present a detailed study on the self-assembly and cytotoxicity of arginine-rich fragments with general form [RF](n) (n = 1-5). These highly simplified sequences, containing only two L-amino acids, provide suitable models for exploring both structure and cytotoxicity features of arginine-based oligopeptides. The organization of the sequences is revealed over a range of length scales, from the nanometer range down to the level of molecular packing, and their cytotoxicity toward C6 rat glioma and RAW264.7 macrophage cell lines is investigated. We found that the polymorphism is dependent on peptide length, with a progressive increase in crystalline ordering upon increasing the number of [RF] pairs along the backbone. A dependence on length was also found for other observables, including critical aggregation concentrations, formation of chiral assemblies and half maximum inhibitory concentrations (IC50). Whereas shorter peptides self-assemble into fractal-like aggregates, clear fibrillogenic capabilities are identified for longer sequences with octameric and decameric chains exhibiting crystalline phases organized into cross-beta structures. Cell viability assays revealed dose-dependent cytotoxicity profiles with very similar behavior for both glioma and macrophage cell lines, which has been interpreted as evidence for a nonspecific mechanism involved in toxicity. We propose that structural organization of [RP](n) peptides plays a paramount role regarding toxicity due to strong increase of local charge density induced by self assemblies rich in cationic groups when interacting with cell membranes.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Rua Botucatu 862,7 Andar, BR-04023062 Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Ciencias Biomed, BR-05508900 Sao Paulo, Brazil
dc.description.affiliationUniv Fed ABC, Ctr Ciencias Nat & Humans, BR-09210580 Santo Andre, Brazil
dc.description.affiliationAalto Univ, Dept Appl Phys, FI-00076 Aalto, Finland
dc.description.affiliationUniv Reading, Dept Chem, Reading RG6 6AD, Berks, England
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Rua Botucatu 862,7 Andar, BR-04023062 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP)
dc.description.sponsorshipCAPES
dc.description.sponsorshipFAPESP
dc.description.sponsorshipEPSRC
dc.description.sponsorshipWolfson Research Merit Award
dc.description.sponsorshipIDFAPESP: 2016/24409-3
dc.description.sponsorshipIDFAPESP: 2015/20216-8, 15/24018-1
dc.description.sponsorshipIDEPSRC: EP/L020599/1
dc.format.extent1/dez
dc.identifierhttp://dx.doi.org/10.1016/j.bpc.2017.11.005
dc.identifier.citationBiophysical Chemistry. Amsterdam, v. 233, p. 44166, 2018.
dc.identifier.doi10.1016/j.bpc.2017.11.005
dc.identifier.issn0301-4622
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54208
dc.identifier.wosWOS:000424184900001
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofBiophysical Chemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectCross-beta structureen
dc.subjectFibrillizationen
dc.subjectCytotoxicityen
dc.subjectScatteringen
dc.subjectFiber diffractionen
dc.titleSequence length dependence in arginine/phenylalanine oligopeptides: Implications for self-assembly and cytotoxicityen
dc.typeinfo:eu-repo/semantics/article
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