A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)

The enzyme Cytochrome P450 aromatase plays an essential role in the biosynthesis of estrogens, and its inhibition is an important target for the development of drugs for the treatment of breast cancer. The main purpose of the present thesis is to improve the understanding of the catalytic mechanism...

Descripción completa

Detalles Bibliográficos
Autor: Viciano Gonzalo, Ignacio
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/392148
Acceso en línea:http://hdl.handle.net/10803/392148
http://dx.doi.org/10.6035/14114.2016.84191
Access Level:acceso abierto
Palabra clave:Aromatase
Compound I
Exemestane
Androstenedione
QM/MM
Hydroxylation
Química Física
544
577
id ES_dd4315ccf0f0678fc7b725297cffbb0e
oai_identifier_str oai:www.tdx.cat:10803/392148
network_acronym_str ES
network_name_str España
repository_id_str
spelling A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)Viciano Gonzalo, IgnacioAromataseCompound IExemestaneAndrostenedioneQM/MMHydroxylationQuímica Física544577The enzyme Cytochrome P450 aromatase plays an essential role in the biosynthesis of estrogens, and its inhibition is an important target for the development of drugs for the treatment of breast cancer. The main purpose of the present thesis is to improve the understanding of the catalytic mechanism and the biochemistry of this enzyme from the standpoint of theoretical chemistry. The results of this thesis have been divided into three main sections: (1) Study of the reactive species of the enzyme aromatase: Compound I; (2) Study of the hydroxylation of the natural substrate androstenedione, during the first catalytic subcycle of the enzyme aromatase; and (3) Study of the hydroxylation of Exemestane, an esteroidal third generation aromatase inhibitor, currently used in hormone dependent breast cancer therapy.La enzima citocromo P450 aromatasa juega un papel esencial en la biosíntesis de estrógenos, y su inhibición es un objetivo importante para el desarrollo de medicamentos para el tratamiento del cáncer de mama. El objetivo principal de la esta Tesis ha sido arrojar luz sobre el mecanismo catalítico y sobre la bioquímica de esta enzima, desde el punto de vista de la química teórica. Los resultados que se presentan en esta Tesis se han dividido en tres secciones principales: (1) Estudio de la especie reactiva de la enzima aromatasa: "Compound I"; (2) Estudio de la hidroxilación del substrato natural androstenediona, a lo largo del primer subciclo catalítico de esta enzima; y (3) Estudio de la hidroxilación del Exemestano, un inhibidor esteroideo de tercera generación de la enzima aromatasa, que se utiliza actualmente en el tratamiento del cáncer de mama hormonodependiente.Universitat Jaume IMartí Forés, SergioCastillo Solsona, RaquelUniversitat Jaume I. Departament de Química Física i Analítica201620162016info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion314 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/392148http://dx.doi.org/10.6035/14114.2016.84191TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by-nc/3.0/es/http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/3921482026-06-14T12:46:07Z
dc.title.none.fl_str_mv A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
title A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
spellingShingle A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
Viciano Gonzalo, Ignacio
Aromatase
Compound I
Exemestane
Androstenedione
QM/MM
Hydroxylation
Química Física
544
577
title_short A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
title_full A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
title_fullStr A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
title_full_unstemmed A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
title_sort A theoretical study on the mechanism of the oxidation of substrates by human aromatase enzyme (CYP19A1)
dc.creator.none.fl_str_mv Viciano Gonzalo, Ignacio
author Viciano Gonzalo, Ignacio
author_facet Viciano Gonzalo, Ignacio
author_role author
dc.contributor.none.fl_str_mv Martí Forés, Sergio
Castillo Solsona, Raquel
Universitat Jaume I. Departament de Química Física i Analítica
dc.subject.none.fl_str_mv Aromatase
Compound I
Exemestane
Androstenedione
QM/MM
Hydroxylation
Química Física
544
577
topic Aromatase
Compound I
Exemestane
Androstenedione
QM/MM
Hydroxylation
Química Física
544
577
description The enzyme Cytochrome P450 aromatase plays an essential role in the biosynthesis of estrogens, and its inhibition is an important target for the development of drugs for the treatment of breast cancer. The main purpose of the present thesis is to improve the understanding of the catalytic mechanism and the biochemistry of this enzyme from the standpoint of theoretical chemistry. The results of this thesis have been divided into three main sections: (1) Study of the reactive species of the enzyme aromatase: Compound I; (2) Study of the hydroxylation of the natural substrate androstenedione, during the first catalytic subcycle of the enzyme aromatase; and (3) Study of the hydroxylation of Exemestane, an esteroidal third generation aromatase inhibitor, currently used in hormone dependent breast cancer therapy.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/392148
http://dx.doi.org/10.6035/14114.2016.84191
url http://hdl.handle.net/10803/392148
http://dx.doi.org/10.6035/14114.2016.84191
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 314 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat Jaume I
publisher.none.fl_str_mv Universitat Jaume I
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421844286668800
score 15.300719

Similares en LA Referencia