Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases
dc.contributor.author
dc.date.accessioned
2019-01-10T10:24:38Z
dc.date.available
2019-01-10T10:24:38Z
dc.date.issued
2018-12-11
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dc.description.abstract
Ribonucleases are proteins whose use is promising in anticancer therapy. We have previously constructed different human pancreatic ribonuclease variants that are selectively cytotoxic for tumor cells by introducing a nuclear localization signal into their sequence. However, these modifications produced an important decrease in their stability compromising their behavior in vivo. Here, we show that we can significantly increase the thermal stability of these cytotoxic proteins by introducing additional disulfide bonds by site-directed mutagenesis. One of these variants increases its thermal stability by around 17 °C, without affecting its catalytic activity while maintaining the cytotoxic activity against tumor cells. We also show that the most stable variant is significantly more resistant to proteolysis when incubated with proteinase K or with human sera, suggesting that its half-live could be increased in vivo once administered
dc.description.sponsorship
This research was funded by MINECO (Spain), grant number BIO2013-43517 and by Universitat de Girona (Spain), grant number MPCU2016/18
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application/pdf
dc.language.iso
eng
dc.publisher
MDPI (Multidisciplinary Digital Publishing Institute)
dc.relation
info:eu-repo/grantAgreement/MINECO//BIO2013-43517-R/ES/RIBONUCLEASAS E INTEINAS COMO HERRAMIENTAS MOLECULARES PARA EL DESARROLLO DE FARMACOS ANTITUMORALES Y ESTUDIO DE PROTEINOPATIAS/
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Reproducció digital del document publicat a: https://doi.org/10.3390/molecules23123273
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Molecules, 2018, vol. 23, núm. 12, p. 3273
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Articles publicats (D-B)
dc.rights
Attribution 4.0 International
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dc.subject
dc.title
Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.contributor.funder
dc.type.peerreviewed
peer-reviewed
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dc.identifier.eissn
1420-3049