Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods

Autores
Jeremias, Hélia F.; Lousa, Diana; Hollmann, Axel; Coelho, Ana C.; Baltazar, Carla S.; Seixas, João D.; Marques, Ana R.; Santos, Nuno C.; Romão, Carlos C.; Soares, Cláudio M.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions of this CORM prototype with BSA, which are dominated by hydrophobic contacts, with a contribution from hydrogen bonding. This kind of information is useful for future CORM design.
Fil: Jeremias, Hélia F.. Universidade Nova de Lisboa; Portugal
Fil: Lousa, Diana. Universidade Nova de Lisboa; Portugal
Fil: Hollmann, Axel. Universidade Nova de Lisboa; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina
Fil: Coelho, Ana C.. Universidade Nova de Lisboa; Portugal
Fil: Baltazar, Carla S.. Universidade Nova de Lisboa; Portugal
Fil: Seixas, João D.. Universidade Nova de Lisboa; Portugal
Fil: Marques, Ana R.. Universidade Nova de Lisboa; Portugal
Fil: Santos, Nuno C.. Universidade Nova de Lisboa; Portugal
Fil: Romão, Carlos C.. Universidade Nova de Lisboa; Portugal
Fil: Soares, Cláudio M.. Universidade Nova de Lisboa; Portugal
Materia
BSA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/231124
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/231124
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methodsJeremias, Hélia F.Lousa, DianaHollmann, AxelCoelho, Ana C.Baltazar, Carla S.Seixas, João D.Marques, Ana R.Santos, Nuno C.Romão, Carlos C.Soares, Cláudio M.BSAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions of this CORM prototype with BSA, which are dominated by hydrophobic contacts, with a contribution from hydrogen bonding. This kind of information is useful for future CORM design.Fil: Jeremias, Hélia F.. Universidade Nova de Lisboa; PortugalFil: Lousa, Diana. Universidade Nova de Lisboa; PortugalFil: Hollmann, Axel. Universidade Nova de Lisboa; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; ArgentinaFil: Coelho, Ana C.. Universidade Nova de Lisboa; PortugalFil: Baltazar, Carla S.. Universidade Nova de Lisboa; PortugalFil: Seixas, João D.. Universidade Nova de Lisboa; PortugalFil: Marques, Ana R.. Universidade Nova de Lisboa; PortugalFil: Santos, Nuno C.. Universidade Nova de Lisboa; PortugalFil: Romão, Carlos C.. Universidade Nova de Lisboa; PortugalFil: Soares, Cláudio M.. Universidade Nova de Lisboa; PortugalPublic Library of Science2018-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/231124Jeremias, Hélia F.; Lousa, Diana; Hollmann, Axel; Coelho, Ana C.; Baltazar, Carla S.; et al.; Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods; Public Library of Science; Plos One; 13; 9; 9-2018; 1-151932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://dx.plos.org/10.1371/journal.pone.0204624info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0204624info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:04:52Zoai:ri.conicet.gov.ar:11336/231124instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:04:53.003CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
title Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
spellingShingle Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
Jeremias, Hélia F.
BSA
title_short Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
title_full Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
title_fullStr Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
title_full_unstemmed Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
title_sort Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods
dc.creator.none.fl_str_mv Jeremias, Hélia F.
Lousa, Diana
Hollmann, Axel
Coelho, Ana C.
Baltazar, Carla S.
Seixas, João D.
Marques, Ana R.
Santos, Nuno C.
Romão, Carlos C.
Soares, Cláudio M.
author Jeremias, Hélia F.
author_facet Jeremias, Hélia F.
Lousa, Diana
Hollmann, Axel
Coelho, Ana C.
Baltazar, Carla S.
Seixas, João D.
Marques, Ana R.
Santos, Nuno C.
Romão, Carlos C.
Soares, Cláudio M.
author_role author
author2 Lousa, Diana
Hollmann, Axel
Coelho, Ana C.
Baltazar, Carla S.
Seixas, João D.
Marques, Ana R.
Santos, Nuno C.
Romão, Carlos C.
Soares, Cláudio M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BSA
topic BSA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions of this CORM prototype with BSA, which are dominated by hydrophobic contacts, with a contribution from hydrogen bonding. This kind of information is useful for future CORM design.
Fil: Jeremias, Hélia F.. Universidade Nova de Lisboa; Portugal
Fil: Lousa, Diana. Universidade Nova de Lisboa; Portugal
Fil: Hollmann, Axel. Universidade Nova de Lisboa; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Centro de Investigación en Biofísica Aplicada y Alimentos. - Universidad Nacional de Santiago del Estero. Centro de Investigación en Biofísica Aplicada y Alimentos; Argentina
Fil: Coelho, Ana C.. Universidade Nova de Lisboa; Portugal
Fil: Baltazar, Carla S.. Universidade Nova de Lisboa; Portugal
Fil: Seixas, João D.. Universidade Nova de Lisboa; Portugal
Fil: Marques, Ana R.. Universidade Nova de Lisboa; Portugal
Fil: Santos, Nuno C.. Universidade Nova de Lisboa; Portugal
Fil: Romão, Carlos C.. Universidade Nova de Lisboa; Portugal
Fil: Soares, Cláudio M.. Universidade Nova de Lisboa; Portugal
description Therapy with inhaled carbon monoxide (CO) is being tested in human clinical trials, yet the alternative use of prodrugs, CO-Releasing Molecules (CORMs), is conceptually advantageous. These molecules are designed to release carbon monoxide in specific tissues, in response to some locally expressed stimulus, where CO can trigger a cytoprotective response. The design of such prodrugs, mostly metal carbonyl complexes, must consider their ADMET profiles, including their interaction with transport plasma proteins. However, the molecular details of this interaction remain elusive. To shed light into this matter, we focused on the CORM prototype [Mo(η 5 -Cp)(CH 2 COOH)(CO) 3 ] (ALF414) and performed a detailed molecular characterization of its interaction with bovine serum albumin (BSA), using spectroscopic and computational methods. The experimental results show that ALF414 partially quenches the intrinsic fluorescence of BSA without changing its secondary structure. The interaction between BSA and ALF414 follows a dynamic quenching mechanism, indicating that no stable complex is formed between the protein Trp residues and ALF414. The molecular dynamics simulations are in good agreement with the experimental results and confirm the dynamic and unspecific character of the interaction between ALF414 and BSA. The simulations also provide important insights into the nature of the interactions of this CORM prototype with BSA, which are dominated by hydrophobic contacts, with a contribution from hydrogen bonding. This kind of information is useful for future CORM design.
publishDate 2018
dc.date.none.fl_str_mv 2018-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/231124
Jeremias, Hélia F.; Lousa, Diana; Hollmann, Axel; Coelho, Ana C.; Baltazar, Carla S.; et al.; Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods; Public Library of Science; Plos One; 13; 9; 9-2018; 1-15
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/231124
identifier_str_mv Jeremias, Hélia F.; Lousa, Diana; Hollmann, Axel; Coelho, Ana C.; Baltazar, Carla S.; et al.; Study of the interactions of bovine serum albumin with a molybdenum(II) carbonyl complex by spectroscopic and molecular simulation methods; Public Library of Science; Plos One; 13; 9; 9-2018; 1-15
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://dx.plos.org/10.1371/journal.pone.0204624
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0204624
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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