Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs
Vanadium complexes (VCs) are promising agents for the treatment, among others, of diabetes and cancer. The development of vanadium-based drugs is mainly limited by a scarce knowledge of the active species in the target organs, which is often determined by the interaction of VCs with biological macro...
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:288837 |
| Acceso en línea: | https://ddd.uab.cat/record/288837 https://dx.doi.org/urn:doi:10.1021/acs.inorgchem.3c01041 |
| Access Level: | acceso abierto |
| Palabra clave: | SDG 3 - Good Health and Well-being |
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Implications of protein interaction in the speciation of potential VIVO-pyridinone drugsFerraro, Giarita|||0000-0001-9385-2429Paolillo, Maddalena|||0000-0001-6289-8862Sciortino, Giuseppe|||0000-0001-9657-1788Pisanu, Federico|||0000-0001-8027-3161Garribba, Eugenio|||0000-0002-7229-5966Merlino, Antonello|||0000-0002-1045-7720SDG 3 - Good Health and Well-beingVanadium complexes (VCs) are promising agents for the treatment, among others, of diabetes and cancer. The development of vanadium-based drugs is mainly limited by a scarce knowledge of the active species in the target organs, which is often determined by the interaction of VCs with biological macromolecules like proteins. Here, we have studied the binding of [VIVO(empp)2] (where Hempp is 1-methyl-2-ethyl-3-hydroxy-4(1H)-pyridinone), an antidiabetic and anticancer VC, with the model protein hen egg white lysozyme (HEWL) by electrospray ionization-mass spectrometry (ESI-MS), electron paramagnetic resonance (EPR), and X-ray crystallography. ESI-MS and EPR techniques reveal that, in aqueous solution, both the species [VIVO(empp)2] and [VIVO(empp)(H2O)]+, derived from the first one upon the loss of a empp(-) ligand, interact with HEWL. Crystallographic data, collected under different experimental conditions, show covalent binding of [VIVO(empp)(H2O)]+ to the side chain of Asp48, and noncovalent binding of cis-[VIVO(empp)2(H2O)], [VIVO(empp)(H2O)]+, [VIVO(empp)(H2O)2]+, and of an unusual trinuclear oxidovanadium(V) complex, [VV3O6(empp)3(H2O)], with accessible sites on the protein surface. The possibility of covalent and noncovalent binding with different strength and of interaction with various sites favor the formation of adducts with the multiple binding of vanadium moieties, allowing the transport in blood and cellular fluids of more than one metal-containing species with a possible amplification of the biological effects. 22023-01-0120232023-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/288837https://dx.doi.org/urn:doi:10.1021/acs.inorgchem.3c01041reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2888372026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| title |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| spellingShingle |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs Ferraro, Giarita|||0000-0001-9385-2429 SDG 3 - Good Health and Well-being |
| title_short |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| title_full |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| title_fullStr |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| title_full_unstemmed |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| title_sort |
Implications of protein interaction in the speciation of potential VIVO-pyridinone drugs |
| dc.creator.none.fl_str_mv |
Ferraro, Giarita|||0000-0001-9385-2429 Paolillo, Maddalena|||0000-0001-6289-8862 Sciortino, Giuseppe|||0000-0001-9657-1788 Pisanu, Federico|||0000-0001-8027-3161 Garribba, Eugenio|||0000-0002-7229-5966 Merlino, Antonello|||0000-0002-1045-7720 |
| author |
Ferraro, Giarita|||0000-0001-9385-2429 |
| author_facet |
Ferraro, Giarita|||0000-0001-9385-2429 Paolillo, Maddalena|||0000-0001-6289-8862 Sciortino, Giuseppe|||0000-0001-9657-1788 Pisanu, Federico|||0000-0001-8027-3161 Garribba, Eugenio|||0000-0002-7229-5966 Merlino, Antonello|||0000-0002-1045-7720 |
| author_role |
author |
| author2 |
Paolillo, Maddalena|||0000-0001-6289-8862 Sciortino, Giuseppe|||0000-0001-9657-1788 Pisanu, Federico|||0000-0001-8027-3161 Garribba, Eugenio|||0000-0002-7229-5966 Merlino, Antonello|||0000-0002-1045-7720 |
| author2_role |
author author author author author |
| dc.subject.none.fl_str_mv |
SDG 3 - Good Health and Well-being |
| topic |
SDG 3 - Good Health and Well-being |
| description |
Vanadium complexes (VCs) are promising agents for the treatment, among others, of diabetes and cancer. The development of vanadium-based drugs is mainly limited by a scarce knowledge of the active species in the target organs, which is often determined by the interaction of VCs with biological macromolecules like proteins. Here, we have studied the binding of [VIVO(empp)2] (where Hempp is 1-methyl-2-ethyl-3-hydroxy-4(1H)-pyridinone), an antidiabetic and anticancer VC, with the model protein hen egg white lysozyme (HEWL) by electrospray ionization-mass spectrometry (ESI-MS), electron paramagnetic resonance (EPR), and X-ray crystallography. ESI-MS and EPR techniques reveal that, in aqueous solution, both the species [VIVO(empp)2] and [VIVO(empp)(H2O)]+, derived from the first one upon the loss of a empp(-) ligand, interact with HEWL. Crystallographic data, collected under different experimental conditions, show covalent binding of [VIVO(empp)(H2O)]+ to the side chain of Asp48, and noncovalent binding of cis-[VIVO(empp)2(H2O)], [VIVO(empp)(H2O)]+, [VIVO(empp)(H2O)2]+, and of an unusual trinuclear oxidovanadium(V) complex, [VV3O6(empp)3(H2O)], with accessible sites on the protein surface. The possibility of covalent and noncovalent binding with different strength and of interaction with various sites favor the formation of adducts with the multiple binding of vanadium moieties, allowing the transport in blood and cellular fluids of more than one metal-containing species with a possible amplification of the biological effects. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2 2023-01-01 2023 2023-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/288837 https://dx.doi.org/urn:doi:10.1021/acs.inorgchem.3c01041 |
| url |
https://ddd.uab.cat/record/288837 https://dx.doi.org/urn:doi:10.1021/acs.inorgchem.3c01041 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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