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Evaluation of the binding of four anti-tumor Casiopeinas to human serum albumin

2017-10Journal article Restricted access
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dc.contributor.authorCorreia, Isabel
dc.contributor.authorBorovic, Sladjana
dc.contributor.authorCavaco, Isabel
dc.contributor.authorMatos, Cristina P.
dc.contributor.authorRoy, Somnath
dc.contributor.authorSantos, Hugo M.
dc.contributor.authorFernandes, Luz
dc.contributor.authorCapelo, Jose L.
dc.contributor.authorRuiz-Azuara, Lena
dc.contributor.authorPessoa, Joao Costa
dc.date.accessioned2019-11-20T15:07:19Z
dc.date.available2019-11-20T15:07:19Z
dc.date.issued2017-10
dc.description.abstractThe metal complexes designated by Casiopeinas (R) are mixed-ligand Cu-II-compounds some of them having promising antineoplastic properties. We report studies of binding of Cu(glycinato)(4,7-dimethyl-1,10-phenanthroline) (Cas-II-Gly (1)), Cu(acetylacetonato)(4,7-dimethy1-1,10-phenanthroline) (Cas-III-Ea (2)), Cu(glycinato) (4,4'-dimethyl-2,2'-bipyridine) (Cas-W-Gly (3)) and Cu(acetylacetonato)(4,4'-dimethyl-2,2'-bipyridine) (Cas-IIIia (4)) to human serum albumin (HSA) by circular dichroism (CD), Electron paramagnetic resonance (EPR) and fluorescence spectroscopy. The results indicate that HSA may bind up to three molecules of the tested Casiopeinas. This is confirmed by inductively coupled plasma atomic absorption spectroscopy measurements of samples of HSA-Casiopeinas after passing by adequate size-exclusion columns. The binding of Cas-II-Gly to HSA was also confirmed by MALDI-TOF mass spectrometric experiments. In the physiological range of concentrations the Casiopeinas form 1:1 adducts with HSA, with conditional binding constants of ca. 1 x 10(9) (1), 4 x 10(7) (2), 1 x 10(6) (3) and 2 x 10(5) (4), values determined from the CD spectra measured, and the fluorescence emission spectra indicates that the binding takes place close to the Trp214 residue. Overall, the data confirm that these Casiopeinas may bind to HSA and may be transported in blood serum by this protein; this might allow some selective tumor targeting, particularly in the case of Cas-Il-Gly. In this work we also discuss aspects associated to the reliability of the frequently used methodologies to determine binding constants based on the measurement of fluorescence emission spectra of solutions containing low concentrations of proteins such as HSA and BSA, by titration with solutions of metal complexes.
dc.description.sponsorshipprogramme Investigador FCT [IF/00100/2013, IF/00007/2015]
dc.description.sponsorshipCONACYT 171991, Mexico
dc.description.sponsorshipBiological Mass Spectrometry Isabel Moura
dc.description.sponsorshipUCIBIO
dc.description.sponsorshipUnidade de Ciencias Biomoleculares Aplicadas [UID/Multi/04378/2013]
dc.description.sponsorshipERDF under the Partnership Agreement [POCI-01-0145-FEDER-007728]
dc.description.sponsorshipAssociate Laboratory for Green Chemistry LAQV [UID/QUI/50006/2013]
dc.description.sponsorshipERDF under the PT Partnership Agreement [POCI-01-0145-FEDER-007265]
dc.identifier.doihttps://doi.org/10.1016/j.jinorgbio.2017.07.025
dc.identifier.issn0162-0134
dc.identifier.urihttp://hdl.handle.net/10400.1/12978
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.subjectCopper(Ii) complexes
dc.subjectDna-binding
dc.subjectAnticancer agents
dc.subjectHeterocyclic bases
dc.subjectCrystal-structures
dc.subjectCleavage activity
dc.subjectLigand-binding
dc.subjectFluorescence
dc.subjectTernary
dc.subject1,10-Phenanthroline
dc.subjectAnti-tumor
dc.subjectHuman serum albumin
dc.subjectBinding constants
dc.subjectCircular dichroism
dc.titleEvaluation of the binding of four anti-tumor Casiopeinas to human serum albumin
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04349%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00100%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FQEQ-QIN%2F0189%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/RECI%2FQEQ-MED%2F0330%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04378%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F50006%2F2013/PT
oaire.citation.endPage297
oaire.citation.startPage284
oaire.citation.titleJournal of Inorganic Biochemistry
oaire.citation.volume175
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNamePALMA ANTUNES CAVACO
person.givenNameISABEL MARIA
person.identifierH-9087-2012
person.identifier.ciencia-idD515-FB5E-1205
person.identifier.orcid0000-0001-8651-9054
project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
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