α-Chymotrypsin catalyses the synthesis of methotrexate oligomers

Detalhes bibliográficos
Autor(a) principal: Noro, Jennifer Martins
Data de Publicação: 2020
Outros Autores: Castro, Tarsila Gabriel, Cavaco-Paulo, Artur, Silva, Carla
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/67065
Resumo: The enzymatic synthesis of methotrexate (MTX) catalysed by ? -chymotrypsin was studied for the first time. The proteolytic enzyme displayed activity for the synthesis of MTX oligomers composed by 6 repeating units (DPavg?=?1.5). For longer oligomers, molecular dynamics simulations confirmed that as the oligomeric chain grows its accommodation in the enzymes active site is hindered, which is evidenced by a decrease of the binding energy associated. The full characterization of the oligomers produced was performed by nuclear magnetic resonance (NMR, 1H and 13C), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF), electrospray ionization (ESI) and differential scanning calorimetry (DSC).
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spelling α-Chymotrypsin catalyses the synthesis of methotrexate oligomersa-chymotrypsinMethotrexateDimersOligomersScience & TechnologyThe enzymatic synthesis of methotrexate (MTX) catalysed by ? -chymotrypsin was studied for the first time. The proteolytic enzyme displayed activity for the synthesis of MTX oligomers composed by 6 repeating units (DPavg?=?1.5). For longer oligomers, molecular dynamics simulations confirmed that as the oligomeric chain grows its accommodation in the enzymes active site is hindered, which is evidenced by a decrease of the binding energy associated. The full characterization of the oligomers produced was performed by nuclear magnetic resonance (NMR, 1H and 13C), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF), electrospray ionization (ESI) and differential scanning calorimetry (DSC).This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/ 04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER- 000004) funded by European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors thanks to FCT for funding their scholarship: Jennifer Noro (SFRH/BD/121673/2016) and Carla Silva (SFRH/IF/00186/2015). Tarsila Castro thanks the senior position funded by the European Union through the European Regional Development Fund (ERDF) under the Competitiveness Operational Program (BioCell-NanoART=Novel Bio-inspired Cellular Nano-architectures, POC-A1.1.4-E-2015 nr. 30/ 01.09.2016). Access to computing resources funded by the Project “Search-ON2: Revitalization of HPC infrastructure of UMinho” (NORTE-07-0162-FEDER-000086), co-funded by the North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF), is also gratefully acknowledged.info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoNoro, Jennifer MartinsCastro, Tarsila GabrielCavaco-Paulo, ArturSilva, Carla2020-01-062020-01-06T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67065engJennifer Noro; Castro, T.; Cavaco-Paulo, Artur; Silva, Carla, -Chymotrypsin catalyses the synthesis of methotrexate oligomers. Process Biochemistry, 98, 193-201, 20201359-51131873-329810.1016/j.procbio.2020.08.004https://www.sciencedirect.com/science/article/pii/S1359511320305171info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:47:37Zoai:repositorium.sdum.uminho.pt:1822/67065Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:45:42.760682Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
title α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
spellingShingle α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
Noro, Jennifer Martins
a-chymotrypsin
Methotrexate
Dimers
Oligomers
Science & Technology
title_short α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
title_full α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
title_fullStr α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
title_full_unstemmed α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
title_sort α-Chymotrypsin catalyses the synthesis of methotrexate oligomers
author Noro, Jennifer Martins
author_facet Noro, Jennifer Martins
Castro, Tarsila Gabriel
Cavaco-Paulo, Artur
Silva, Carla
author_role author
author2 Castro, Tarsila Gabriel
Cavaco-Paulo, Artur
Silva, Carla
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Noro, Jennifer Martins
Castro, Tarsila Gabriel
Cavaco-Paulo, Artur
Silva, Carla
dc.subject.por.fl_str_mv a-chymotrypsin
Methotrexate
Dimers
Oligomers
Science & Technology
topic a-chymotrypsin
Methotrexate
Dimers
Oligomers
Science & Technology
description The enzymatic synthesis of methotrexate (MTX) catalysed by ? -chymotrypsin was studied for the first time. The proteolytic enzyme displayed activity for the synthesis of MTX oligomers composed by 6 repeating units (DPavg?=?1.5). For longer oligomers, molecular dynamics simulations confirmed that as the oligomeric chain grows its accommodation in the enzymes active site is hindered, which is evidenced by a decrease of the binding energy associated. The full characterization of the oligomers produced was performed by nuclear magnetic resonance (NMR, 1H and 13C), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF), electrospray ionization (ESI) and differential scanning calorimetry (DSC).
publishDate 2020
dc.date.none.fl_str_mv 2020-01-06
2020-01-06T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/67065
url http://hdl.handle.net/1822/67065
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Jennifer Noro; Castro, T.; Cavaco-Paulo, Artur; Silva, Carla, -Chymotrypsin catalyses the synthesis of methotrexate oligomers. Process Biochemistry, 98, 193-201, 2020
1359-5113
1873-3298
10.1016/j.procbio.2020.08.004
https://www.sciencedirect.com/science/article/pii/S1359511320305171
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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