Towards predictable transmembrane transport: QSAR analysis of anion binding and transport
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/19223 |
Resumo: | The transport of anions across biological membranes by small molecules is a growing research field due to the potential therapeutic benefits of these compounds. However, little is known about the exact mechanism by which these drug-like molecules work and which molecular features make a good transporter. An extended series of 1-hexyl-3-phenylthioureas were synthesized, fully characterized (NMR, mass spectrometry, IR and single crystal diffraction) and their anion binding and anion transport properties were assessed using H-1 NMR titration techniques and a variety of vesicle-based experiments. Quantitative structure-activity relationship (QSAR) analysis revealed that the anion binding abilities of the mono-thioureas are dominated by the (hydrogen bond) acidity of the thiourea NH function. Furthermore, mathematical models show that the experimental transmembrane anion transport ability is mainly dependent on the lipophilicity of the transporter (partitioning into the membrane), but smaller contributions of molecular size (diffusion) and hydrogen bond acidity (anion binding) were also present. Finally, we provide the first step towards predictable anion transport by employing the QSAR equations to estimate the transmembrane transport ability of four new compounds. |
id |
RCAP_ef6af0e94be5ab459faca0b66941596c |
---|---|
oai_identifier_str |
oai:ria.ua.pt:10773/19223 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transportCHLORIDE TRANSPORTMEMBRANE TRANSPORTERSCELL-MEMBRANESFLIP-FLOPRECEPTORSVESICLERECOGNITIONPRODIGIOSINSCOEFFICIENTSPARAMETERSThe transport of anions across biological membranes by small molecules is a growing research field due to the potential therapeutic benefits of these compounds. However, little is known about the exact mechanism by which these drug-like molecules work and which molecular features make a good transporter. An extended series of 1-hexyl-3-phenylthioureas were synthesized, fully characterized (NMR, mass spectrometry, IR and single crystal diffraction) and their anion binding and anion transport properties were assessed using H-1 NMR titration techniques and a variety of vesicle-based experiments. Quantitative structure-activity relationship (QSAR) analysis revealed that the anion binding abilities of the mono-thioureas are dominated by the (hydrogen bond) acidity of the thiourea NH function. Furthermore, mathematical models show that the experimental transmembrane anion transport ability is mainly dependent on the lipophilicity of the transporter (partitioning into the membrane), but smaller contributions of molecular size (diffusion) and hydrogen bond acidity (anion binding) were also present. Finally, we provide the first step towards predictable anion transport by employing the QSAR equations to estimate the transmembrane transport ability of four new compounds.ROYAL SOC CHEMISTRY2017-12-07T19:05:12Z2013-01-01T00:00:00Z2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/19223eng2041-652010.1039/c3sc51023aBusschaert, NathalieBradberry, Samuel J.Wenzel, MarcoHaynes, Cally J. E.Hiscock, Jennifer R.Kirby, Isabelle L.Karagiannidis, Louise E.Moore, Stephen J.Wells, Neil J.Herniman, JulieLangley, G. JohnHorton, Peter N.Light, Mark E.Marques, IgorCosta, Paulo J.Felix, VitorFrey, Jeremy G.Gale, Philip A.info: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:RCAAP2024-02-22T11:37:17Zoai:ria.ua.pt:10773/19223Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:54:02.128041Repositório 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 |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
title |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
spellingShingle |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport Busschaert, Nathalie CHLORIDE TRANSPORT MEMBRANE TRANSPORTERS CELL-MEMBRANES FLIP-FLOP RECEPTORS VESICLE RECOGNITION PRODIGIOSINS COEFFICIENTS PARAMETERS |
title_short |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
title_full |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
title_fullStr |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
title_full_unstemmed |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
title_sort |
Towards predictable transmembrane transport: QSAR analysis of anion binding and transport |
author |
Busschaert, Nathalie |
author_facet |
Busschaert, Nathalie Bradberry, Samuel J. Wenzel, Marco Haynes, Cally J. E. Hiscock, Jennifer R. Kirby, Isabelle L. Karagiannidis, Louise E. Moore, Stephen J. Wells, Neil J. Herniman, Julie Langley, G. John Horton, Peter N. Light, Mark E. Marques, Igor Costa, Paulo J. Felix, Vitor Frey, Jeremy G. Gale, Philip A. |
author_role |
author |
author2 |
Bradberry, Samuel J. Wenzel, Marco Haynes, Cally J. E. Hiscock, Jennifer R. Kirby, Isabelle L. Karagiannidis, Louise E. Moore, Stephen J. Wells, Neil J. Herniman, Julie Langley, G. John Horton, Peter N. Light, Mark E. Marques, Igor Costa, Paulo J. Felix, Vitor Frey, Jeremy G. Gale, Philip A. |
author2_role |
author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Busschaert, Nathalie Bradberry, Samuel J. Wenzel, Marco Haynes, Cally J. E. Hiscock, Jennifer R. Kirby, Isabelle L. Karagiannidis, Louise E. Moore, Stephen J. Wells, Neil J. Herniman, Julie Langley, G. John Horton, Peter N. Light, Mark E. Marques, Igor Costa, Paulo J. Felix, Vitor Frey, Jeremy G. Gale, Philip A. |
dc.subject.por.fl_str_mv |
CHLORIDE TRANSPORT MEMBRANE TRANSPORTERS CELL-MEMBRANES FLIP-FLOP RECEPTORS VESICLE RECOGNITION PRODIGIOSINS COEFFICIENTS PARAMETERS |
topic |
CHLORIDE TRANSPORT MEMBRANE TRANSPORTERS CELL-MEMBRANES FLIP-FLOP RECEPTORS VESICLE RECOGNITION PRODIGIOSINS COEFFICIENTS PARAMETERS |
description |
The transport of anions across biological membranes by small molecules is a growing research field due to the potential therapeutic benefits of these compounds. However, little is known about the exact mechanism by which these drug-like molecules work and which molecular features make a good transporter. An extended series of 1-hexyl-3-phenylthioureas were synthesized, fully characterized (NMR, mass spectrometry, IR and single crystal diffraction) and their anion binding and anion transport properties were assessed using H-1 NMR titration techniques and a variety of vesicle-based experiments. Quantitative structure-activity relationship (QSAR) analysis revealed that the anion binding abilities of the mono-thioureas are dominated by the (hydrogen bond) acidity of the thiourea NH function. Furthermore, mathematical models show that the experimental transmembrane anion transport ability is mainly dependent on the lipophilicity of the transporter (partitioning into the membrane), but smaller contributions of molecular size (diffusion) and hydrogen bond acidity (anion binding) were also present. Finally, we provide the first step towards predictable anion transport by employing the QSAR equations to estimate the transmembrane transport ability of four new compounds. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-01-01T00:00:00Z 2013 2017-12-07T19:05:12Z |
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/10773/19223 |
url |
http://hdl.handle.net/10773/19223 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-6520 10.1039/c3sc51023a |
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 |
ROYAL SOC CHEMISTRY |
publisher.none.fl_str_mv |
ROYAL SOC CHEMISTRY |
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 |
|
_version_ |
1799137592442093568 |