Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
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/10451/23431 |
Resumo: | © 2014 Wiley Periodicals, Inc. |
id |
RCAP_7cb149ed18013d8fbbcc514191b5708b |
---|---|
oai_identifier_str |
oai:repositorio.ul.pt:10451/23431 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivativesAnalgesiaBarrierKyotorphinLipophilicityPermeability© 2014 Wiley Periodicals, Inc.Amidated kyotorphin (L-Tyr-L-Arg-NH2; KTP-NH2) causes analgesia when systemically administered. The lipophilic ibuprofen-conjugated derivative of KTP-NH2 has improved analgesic efficacy. However, fast degradation by peptidases impacts negatively in the pharmacodynamics of these drugs. In this work, selected derivatives of KTP and KTP-NH2 were synthesized to combine lipophilicity and resistance to enzymatic degradation. Eight novel structural modifications were tested for the potential to transverse lipid membranes and to evaluate their efficacy in vivo. The rationale behind the design of the pool of the eight selected molecules consisted in the addition of individual group atthe N-terminus, namely the tert-butyloxycarbonyl (Boc), -aminobutyric acid (GABA), acetyl, butanoyl, and propanoyl or in the substitution of the tyrosine residue by an indole moiety and in the replacement of the peptidic bond by a urea-like bond in some cases. All the drugs used in the study are intrinsically fluorescent, which enables the use of spectrofluorimetry to sample the drugs in the permeation assays. The results show that the BOC and indolyl derivatives of KTP-NH2 have maximal ability to permeate membranes with concomitant maximal analgesic power. Overall, the results demonstrate that membrane permeation is correlated with analgesic efficacy. However, this is not the only factor accounting for analgesia. KTP-NH2 for instance has low passive permeation but is known to have central action. In this case, hypothetical transcytosis over the blood-brain barrier seems to depend on dipeptide transporters.Isa D. Serrano and Vasanthakumar G. Ramu contributed equally to this work Contract grant sponsor: Fundação para a Ciência e Tecnologia–Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal), EC-FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP) Contract grant number: 230654, PTDC/QUI/69937/2006, PTDC/QUI-BIQ/112929/2009 Contract grant sponsor: FP7-PEOPLE IRSES (International Research Staff Exchange Scheme) project MEMPEPACROSS Contract grant sponsor: FCT-MCTES Contract grant number: SFRH/BPD/37998/2007, PTDC/QUIBIQ/114774/2009, SFRH/BD/70423/2010WileyRepositório da Universidade de LisboaSerrano, Isa D.Ramu, Vasanthakumar G.Pinto, Antónia R. T.Freire, João M.Tavares, IsauraHeras, MontserratBardaji, Eduard R.Castanho, Miguel A. R. B.2016-04-18T16:12:05Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/23431engPeptideScience Volume 104 / Number 10006-352510.1002/bip.22580metadata only accessinfo: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:RCAAP2023-11-08T16:10:57Zoai:repositorio.ul.pt:10451/23431Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:40:35.039386Repositório 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 |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
title |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
spellingShingle |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives Serrano, Isa D. Analgesia Barrier Kyotorphin Lipophilicity Permeability |
title_short |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
title_full |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
title_fullStr |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
title_full_unstemmed |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
title_sort |
Correlation between membrane translocation and analgesic efficacy in kyotorphin derivatives |
author |
Serrano, Isa D. |
author_facet |
Serrano, Isa D. Ramu, Vasanthakumar G. Pinto, Antónia R. T. Freire, João M. Tavares, Isaura Heras, Montserrat Bardaji, Eduard R. Castanho, Miguel A. R. B. |
author_role |
author |
author2 |
Ramu, Vasanthakumar G. Pinto, Antónia R. T. Freire, João M. Tavares, Isaura Heras, Montserrat Bardaji, Eduard R. Castanho, Miguel A. R. B. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Serrano, Isa D. Ramu, Vasanthakumar G. Pinto, Antónia R. T. Freire, João M. Tavares, Isaura Heras, Montserrat Bardaji, Eduard R. Castanho, Miguel A. R. B. |
dc.subject.por.fl_str_mv |
Analgesia Barrier Kyotorphin Lipophilicity Permeability |
topic |
Analgesia Barrier Kyotorphin Lipophilicity Permeability |
description |
© 2014 Wiley Periodicals, Inc. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z 2016-04-18T16:12:05Z |
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/10451/23431 |
url |
http://hdl.handle.net/10451/23431 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PeptideScience Volume 104 / Number 1 0006-3525 10.1002/bip.22580 |
dc.rights.driver.fl_str_mv |
metadata only access info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
metadata only access |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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_ |
1799134315066425344 |