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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/231124
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/231124 |
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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 Técnicas2025-09-29T10:07:45Zoai: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:34982025-09-29 10:07:45.496CONICET 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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1844613941644230656 |
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13.070432 |