Towards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype

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Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversity of Vila Velha-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorKU Leuven-
Autor(es): dc.contributorUniversidade Federal de Uberlândia (UFU)-
Autor(es): dc.creatorPinheiro-Junior, Ernesto Lopes-
Autor(es): dc.creatorBoldrini-França, Johara-
Autor(es): dc.creatorTakeda, Agnes Alessandra Sekijima [UNESP]-
Autor(es): dc.creatorCosta, Tássia Rafaella-
Autor(es): dc.creatorPeigneur, Steve-
Autor(es): dc.creatorCardoso, Iara Aimê-
Autor(es): dc.creatorOliveira, Isadora Sousa de-
Autor(es): dc.creatorSampaio, Suely Vilela-
Autor(es): dc.creatorde Mattos Fontes, Marcos Roberto [UNESP]-
Autor(es): dc.creatorTytgat, Jan-
Autor(es): dc.creatorArantes, Eliane Candiani-
Data de aceite: dc.date.accessioned2022-08-04T22:12:21Z-
Data de disponibilização: dc.date.available2022-08-04T22:12:21Z-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2021-10-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.ijbiomac.2021.09.004-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/222384-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/222384-
Descrição: dc.descriptionPEGylation was firstly described around 50 years ago and has been used for more than 30 years as a strategy to improve the drugability of biopharmaceuticals. However, it remains poorly employed in toxinology, even though it may be a promising strategy to empower these compounds in therapeutics. This work reports the PEGylation of rCollinein-1, a recombinant snake venom serine protease (SVSP), able to degrade fibrinogen and inhibit the hEAG1 potassium channel. We compared the functional, structural, and immunogenic properties of the non-PEGylated (rCollinein-1) and PEGylated (PEG-rCollinein-1) forms. PEG-rCollinein-1 shares similar kinetic parameters with rCollinein-1, maintaining its capability of degrading fibrinogen, but with reduced activity on hEAG1 channel. CD analysis revealed the maintenance of protein conformation after PEGylation, and thermal shift assays demonstrated similar thermostability. Both forms of the enzyme showed to be non-toxic to peripheral blood mononuclear cells (PBMC). In silico epitope prediction indicated three putative immunogenic peptides. However, immune response on mice showed PEG-rCollinein-1 was devoid of immunogenicity. PEGylation directed rCollinein-1 activity towards hemostasis control, broadening its possibilities to be employed as a defibrinogenant agent.-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionFonds Wetenschappelijk Onderzoek-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionKU Leuven-
Descrição: dc.descriptionVlaamse regering-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo, Av. do Café s/n°-
Descrição: dc.descriptionUniversity of Vila Velha, Av. Comissário José Dantas de Melo, 21, Boa Vista II-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionToxicology and Pharmacology KU Leuven, O&N II Herestraat 49 - PO box 922-
Descrição: dc.descriptionInstitute of Biotechnology Federal University of Uberlandia-
Descrição: dc.descriptionDepartment of Biophysics and Pharmacology Institute of Biosciences São Paulo State University (UNESP)-
Descrição: dc.descriptionFAPESP: 2011/23236-4-
Descrição: dc.descriptionFAPESP: 2015/17286-0-
Descrição: dc.descriptionFAPESP: 2015/18432-0-
Descrição: dc.descriptionCNPq: 302883/2017-7-
Descrição: dc.descriptionCNPq: 307155/2017-0-
Descrição: dc.descriptionKU Leuven: CELSA 17/047-
Descrição: dc.descriptionVlaamse regering: GOA4919N-
Descrição: dc.descriptionVlaamse regering: GOC2319N-
Descrição: dc.descriptionVlaamse regering: GOE7120N-
Descrição: dc.descriptionKU Leuven: PDM/19/164-
Formato: dc.format564-573-
Idioma: dc.languageen-
Relação: dc.relationInternational Journal of Biological Macromolecules-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCrotalus durissus collilineatus-
Palavras-chave: dc.subjectPEGylation-
Palavras-chave: dc.subjectSnake venom thrombin-like enzyme-
Título: dc.titleTowards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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