Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases

Autores
Nigro, Mariano; Sánchez Moreno, Israél; Benito Arenas, Raúl; Valino, Ana Laura; Iribarren, Adolfo Marcelo; Veiga, Nicolás; García Junceda, Eduardo; Lewkowicz, Elizabeth Sandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed.
Fil: Nigro, Mariano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina
Fil: Sánchez Moreno, Israél. Consejo Superior de Investigaciones Científicas; España
Fil: Benito Arenas, Raúl. Consejo Superior de Investigaciones Científicas; España
Fil: Valino, Ana Laura. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina
Fil: Veiga, Nicolás. Universidad de la República. Facultad de Química; Uruguay
Fil: García Junceda, Eduardo. Consejo Superior de Investigaciones Científicas; España
Fil: Lewkowicz, Elizabeth Sandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
aldol reaction
biocatalysis
drug design
stereoselectivity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/239060
Acceder
id CONICETDig_60263684286303e48544a005e8837abb
oai_identifier_str oai:ri.conicet.gov.ar:11336/239060
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent AldolasesNigro, MarianoSánchez Moreno, IsraélBenito Arenas, RaúlValino, Ana LauraIribarren, Adolfo MarceloVeiga, NicolásGarcía Junceda, EduardoLewkowicz, Elizabeth Sandraaldol reactionbiocatalysisdrug designstereoselectivityhttps://purl.org/becyt/ford/2.9https://purl.org/becyt/ford/2Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed.Fil: Nigro, Mariano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; ArgentinaFil: Sánchez Moreno, Israél. Consejo Superior de Investigaciones Científicas; EspañaFil: Benito Arenas, Raúl. Consejo Superior de Investigaciones Científicas; EspañaFil: Valino, Ana Laura. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; ArgentinaFil: Veiga, Nicolás. Universidad de la República. Facultad de Química; UruguayFil: García Junceda, Eduardo. Consejo Superior de Investigaciones Científicas; EspañaFil: Lewkowicz, Elizabeth Sandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2024-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/239060Nigro, Mariano; Sánchez Moreno, Israél; Benito Arenas, Raúl; Valino, Ana Laura; Iribarren, Adolfo Marcelo; et al.; Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases; MDPI; Biomolecules; 14; 7; 6-2024; 1-242218-273XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/biom14070750info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:00:23Zoai:ri.conicet.gov.ar:11336/239060instacron: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:34982025-09-17 11:00:23.635CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
title Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
spellingShingle Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
Nigro, Mariano
aldol reaction
biocatalysis
drug design
stereoselectivity
title_short Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
title_full Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
title_fullStr Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
title_full_unstemmed Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
title_sort Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases
dc.creator.none.fl_str_mv Nigro, Mariano
Sánchez Moreno, Israél
Benito Arenas, Raúl
Valino, Ana Laura
Iribarren, Adolfo Marcelo
Veiga, Nicolás
García Junceda, Eduardo
Lewkowicz, Elizabeth Sandra
author Nigro, Mariano
author_facet Nigro, Mariano
Sánchez Moreno, Israél
Benito Arenas, Raúl
Valino, Ana Laura
Iribarren, Adolfo Marcelo
Veiga, Nicolás
García Junceda, Eduardo
Lewkowicz, Elizabeth Sandra
author_role author
author2 Sánchez Moreno, Israél
Benito Arenas, Raúl
Valino, Ana Laura
Iribarren, Adolfo Marcelo
Veiga, Nicolás
García Junceda, Eduardo
Lewkowicz, Elizabeth Sandra
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv aldol reaction
biocatalysis
drug design
stereoselectivity
topic aldol reaction
biocatalysis
drug design
stereoselectivity
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.9
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed.
Fil: Nigro, Mariano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina
Fil: Sánchez Moreno, Israél. Consejo Superior de Investigaciones Científicas; España
Fil: Benito Arenas, Raúl. Consejo Superior de Investigaciones Científicas; España
Fil: Valino, Ana Laura. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina
Fil: Veiga, Nicolás. Universidad de la República. Facultad de Química; Uruguay
Fil: García Junceda, Eduardo. Consejo Superior de Investigaciones Científicas; España
Fil: Lewkowicz, Elizabeth Sandra. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Dihydroxyacetone phosphate (DHAP)-dependent aldolases catalyze the aldol addition of DHAP to a variety of aldehydes and generate compounds with two stereocenters. This reaction is useful to synthesize chiral acyclic nucleosides, which constitute a well-known class of antiviral drugs currently used. In such compounds, the chirality of the aliphatic chain, which mimics the open pentose residue, is crucial for activity. In this work, three DHAP-dependent aldolases: fructose-1,6-biphosphate aldolase from rabbit muscle, rhanmulose-1-phosphate aldolase from Thermotoga maritima, and fuculose-1-phosphate aldolase from Escherichia coli, were used as biocatalysts. Aldehyde derivatives of thymine and cytosine were used as acceptor substrates, generating new acyclic nucleoside analogues containing two new stereocenters with conversion yields between 70% and 90%. Moreover, structural analyses by molecular docking were carried out to gain insights into the diasteromeric excess observed.
publishDate 2024
dc.date.none.fl_str_mv 2024-06
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/11336/239060
Nigro, Mariano; Sánchez Moreno, Israél; Benito Arenas, Raúl; Valino, Ana Laura; Iribarren, Adolfo Marcelo; et al.; Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases; MDPI; Biomolecules; 14; 7; 6-2024; 1-24
2218-273X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/239060
identifier_str_mv Nigro, Mariano; Sánchez Moreno, Israél; Benito Arenas, Raúl; Valino, Ana Laura; Iribarren, Adolfo Marcelo; et al.; Synthesis of Chiral Acyclic Pyrimidine Nucleoside Analogues from DHAP-Dependent Aldolases; MDPI; Biomolecules; 14; 7; 6-2024; 1-24
2218-273X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/biom14070750
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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
_version_ 1843606293558853632
score 13.001348

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