Biological and conformational evaluation of angiotensin II lactam bridge containing analogues
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/34328 http://dx.doi.org/10.1016/j.regpep.2011.05.015 |
Resumo: | Angiotensin II (All) is the active octapeptide product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. in an attempt to establish the All-receptor-bound conformation of this octapeptide, we designed conformationally constrained analogues by scanning the entire All sequence with an i-(i+2) and i-(i + 3) lactam bridge consisting of an Asp-(Xaa)(n)-Lys scaffold. Most analogues presented low agonistic activity when compared to All in the different bioassays tested. the exceptions are cyclo(0-1a) [Asp(0), endo-(Lys(1a))]-All (1) and [Asp(0), endo-(Lys(1a))]-All (2), both of which showed activity similar to All. Based on peptide 1 and the analogue cyclo(3-5)[Sar(1), Asp(3), Lys(5)]-All characterized by Matsoukas et al., we analyzed the agonistic and antagonistic activities, respectively, through a new monocyclic peptide series synthesized by using the following combinations of residues as bridgehead elements for the lactam bond formation: D- or L-Asp combined with D- or L-Lys or L-Glu combined with L-Orn. Six analogues showed an approximately 20% increase in biological activity when compared with peptide (1) and were equipotent to All. in contrast, six analogues presented antagonistic activity. These results suggest that the position of the lactam bridge is more important than the bridge length or chirality for recognition of and binding to the angiotensin 11 AT1-receptor. (C) 2011 Elsevier B.V. All rights reserved. |
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Oliveira Junior, Vani XavierFázio, Marcos Antonio [UNIFESP]Silva, Adriana FariasCampana, Patricia TargonPesquero, João Bosco [UNIFESP]Santos, Edson LucasCosta-Neto, Cláudio MiguelMiranda, Antonio [UNIFESP]Universidade Federal do ABC (UFABC)Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo (USP)Fundacao Univ Fed Grande Dourados2016-01-24T14:17:34Z2016-01-24T14:17:34Z2011-12-10Regulatory Peptides. Amsterdam: Elsevier B.V., v. 172, n. 1-3, p. 1-7, 2011.0167-0115http://repositorio.unifesp.br/handle/11600/34328http://dx.doi.org/10.1016/j.regpep.2011.05.015WOS000296176100001.pdf10.1016/j.regpep.2011.05.015WOS:000296176100001Angiotensin II (All) is the active octapeptide product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. in an attempt to establish the All-receptor-bound conformation of this octapeptide, we designed conformationally constrained analogues by scanning the entire All sequence with an i-(i+2) and i-(i + 3) lactam bridge consisting of an Asp-(Xaa)(n)-Lys scaffold. Most analogues presented low agonistic activity when compared to All in the different bioassays tested. the exceptions are cyclo(0-1a) [Asp(0), endo-(Lys(1a))]-All (1) and [Asp(0), endo-(Lys(1a))]-All (2), both of which showed activity similar to All. Based on peptide 1 and the analogue cyclo(3-5)[Sar(1), Asp(3), Lys(5)]-All characterized by Matsoukas et al., we analyzed the agonistic and antagonistic activities, respectively, through a new monocyclic peptide series synthesized by using the following combinations of residues as bridgehead elements for the lactam bond formation: D- or L-Asp combined with D- or L-Lys or L-Glu combined with L-Orn. Six analogues showed an approximately 20% increase in biological activity when compared with peptide (1) and were equipotent to All. in contrast, six analogues presented antagonistic activity. These results suggest that the position of the lactam bridge is more important than the bridge length or chirality for recognition of and binding to the angiotensin 11 AT1-receptor. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniv São Paulo, Escola Artes Ciencias & Humanidades, BR-03828000 São Paulo, BrazilFundacao Univ Fed Grande Dourados, Fac Ciencias Biol & Ambientais, BR-79804970 Dourados, MS, BrazilUniv São Paulo, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Science1-7engElsevier B.V.Regulatory Peptideshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policyinfo:eu-repo/semantics/openAccessAngiotensin IILactam bridgeSARMicrophysiometerSPPSCircular dichroismBiological and conformational evaluation of angiotensin II lactam bridge containing analoguesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000296176100001.pdfapplication/pdf442464${dspace.ui.url}/bitstream/11600/34328/1/WOS000296176100001.pdff45dd61de6bd24584f87dfd7b738a8ceMD51open accessTEXTWOS000296176100001.pdf.txtWOS000296176100001.pdf.txtExtracted texttext/plain46652${dspace.ui.url}/bitstream/11600/34328/2/WOS000296176100001.pdf.txt3823cccf976520496c642c121dce9e3dMD52open access11600/343282022-06-02 09:20:54.867open accessoai:repositorio.unifesp.br:11600/34328Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:15:16.914108Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
title |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
spellingShingle |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues Oliveira Junior, Vani Xavier Angiotensin II Lactam bridge SAR Microphysiometer SPPS Circular dichroism |
title_short |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
title_full |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
title_fullStr |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
title_full_unstemmed |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
title_sort |
Biological and conformational evaluation of angiotensin II lactam bridge containing analogues |
author |
Oliveira Junior, Vani Xavier |
author_facet |
Oliveira Junior, Vani Xavier Fázio, Marcos Antonio [UNIFESP] Silva, Adriana Farias Campana, Patricia Targon Pesquero, João Bosco [UNIFESP] Santos, Edson Lucas Costa-Neto, Cláudio Miguel Miranda, Antonio [UNIFESP] |
author_role |
author |
author2 |
Fázio, Marcos Antonio [UNIFESP] Silva, Adriana Farias Campana, Patricia Targon Pesquero, João Bosco [UNIFESP] Santos, Edson Lucas Costa-Neto, Cláudio Miguel Miranda, Antonio [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal do ABC (UFABC) Universidade Federal de São Paulo (UNIFESP) Universidade de São Paulo (USP) Fundacao Univ Fed Grande Dourados |
dc.contributor.author.fl_str_mv |
Oliveira Junior, Vani Xavier Fázio, Marcos Antonio [UNIFESP] Silva, Adriana Farias Campana, Patricia Targon Pesquero, João Bosco [UNIFESP] Santos, Edson Lucas Costa-Neto, Cláudio Miguel Miranda, Antonio [UNIFESP] |
dc.subject.eng.fl_str_mv |
Angiotensin II Lactam bridge SAR Microphysiometer SPPS Circular dichroism |
topic |
Angiotensin II Lactam bridge SAR Microphysiometer SPPS Circular dichroism |
description |
Angiotensin II (All) is the active octapeptide product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. in an attempt to establish the All-receptor-bound conformation of this octapeptide, we designed conformationally constrained analogues by scanning the entire All sequence with an i-(i+2) and i-(i + 3) lactam bridge consisting of an Asp-(Xaa)(n)-Lys scaffold. Most analogues presented low agonistic activity when compared to All in the different bioassays tested. the exceptions are cyclo(0-1a) [Asp(0), endo-(Lys(1a))]-All (1) and [Asp(0), endo-(Lys(1a))]-All (2), both of which showed activity similar to All. Based on peptide 1 and the analogue cyclo(3-5)[Sar(1), Asp(3), Lys(5)]-All characterized by Matsoukas et al., we analyzed the agonistic and antagonistic activities, respectively, through a new monocyclic peptide series synthesized by using the following combinations of residues as bridgehead elements for the lactam bond formation: D- or L-Asp combined with D- or L-Lys or L-Glu combined with L-Orn. Six analogues showed an approximately 20% increase in biological activity when compared with peptide (1) and were equipotent to All. in contrast, six analogues presented antagonistic activity. These results suggest that the position of the lactam bridge is more important than the bridge length or chirality for recognition of and binding to the angiotensin 11 AT1-receptor. (C) 2011 Elsevier B.V. All rights reserved. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-12-10 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:17:34Z |
dc.date.available.fl_str_mv |
2016-01-24T14:17:34Z |
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.citation.fl_str_mv |
Regulatory Peptides. Amsterdam: Elsevier B.V., v. 172, n. 1-3, p. 1-7, 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/34328 http://dx.doi.org/10.1016/j.regpep.2011.05.015 |
dc.identifier.issn.none.fl_str_mv |
0167-0115 |
dc.identifier.file.none.fl_str_mv |
WOS000296176100001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1016/j.regpep.2011.05.015 |
dc.identifier.wos.none.fl_str_mv |
WOS:000296176100001 |
identifier_str_mv |
Regulatory Peptides. Amsterdam: Elsevier B.V., v. 172, n. 1-3, p. 1-7, 2011. 0167-0115 WOS000296176100001.pdf 10.1016/j.regpep.2011.05.015 WOS:000296176100001 |
url |
http://repositorio.unifesp.br/handle/11600/34328 http://dx.doi.org/10.1016/j.regpep.2011.05.015 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Regulatory Peptides |
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http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-7 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
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