Repository logo
 
Publication

Structure-function studies of BPP-BrachyNH 2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

2017Journal article Open access
Simple item page
dc.contributor.authorArcanjo, Daniel D.R.
dc.contributor.authorVasconcelos, Andreanne G.
dc.contributor.authorNascimento, Lucas A.
dc.contributor.authorMafud, Ana Carolina
dc.contributor.authorPlácido, Alexandra
dc.contributor.authorAlves, Michel M.M.
dc.contributor.authorDelerue-Matos, Cristina
dc.contributor.authorBemquerer, Marcelo P.
dc.contributor.authorVale, Nuno
dc.contributor.authorGomes, Paula
dc.contributor.authorOliveira, Eduardo B.
dc.contributor.authorLima, Francisco C.A.
dc.contributor.authorMascarenhas, Yvonne P.
dc.contributor.authorCarvalho, Fernando Aécio A.
dc.contributor.authorSimonsen, Ulf
dc.contributor.authorRamos, Ricardo M.
dc.contributor.authorLeite, José Roberto S.A.
dc.date.accessioned2019-04-12T13:07:26Z
dc.date.available2019-04-12T13:07:26Z
dc.date.issued2017
dc.description.abstractThe vasoactive proline-rich oligopeptide termed BPP-BrachyNH2 (H-WPPPKVSP-NH2) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH2 was investigated in order to predict which structural components are important or required for interaction with ACE. Furthermore, the toxicological profile was assessed by in silico prediction and in vitro MTT assay. Two BPP-BrachyNH2 analogues (des-Trp1-BPP-BrachyNH2 and des-Pro8-BPP-BrachyNH2) were synthesized, and in vitro and in silico ACE inhibitory activity and toxicological profile were assessed. The des-Trp1-BPP-BrachyNH2 and des-Pro8-BPP-BrachyNH2 were respectively 3.2- and 29.5-fold less active than the BPP-BrachyNH2-induced ACE inhibitory activity. Molecular Dynamic and Molecular Mechanics Poisson-Boltzmann Surface Area simulations (MM-PBSA) demonstrated that the ACE/BBP-BrachyNH2 complex showed lower binding and van der Wall energies than the ACE/des-Pro8-BPP-BrachyNH2 complex, therefore having better stability. The removal of the N-terminal tryptophan increased the in silico predicted toxicological effects and cytotoxicity when compared with BPP-BrachyNH2 or des-Pro8-BPP-BrachyNH2. Otherwise, des-Pro8-BPP-BrachyNH2 was 190-fold less cytotoxic than BPP-BrachyNH2. Thus, the removal of C-terminal proline residue was able to markedly decrease both the BPP-BrachyNH2-induced ACE inhibitory and cytotoxic effects assessed by in vitro and in silico approaches. In conclusion, the aminoacid sequence of BPP-BrachyNH2 is essential for its ACE inhibitory activity and associated with an acceptable toxicological profile. The perspective of the interactions of BPP-BrachyNH2 with ACE found in the present study can be used for development of drugs with differential therapeutic profile than current ACE inhibitors.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejmech.2017.08.019pt_PT
dc.identifier.issn0223-5234
dc.identifier.urihttp://hdl.handle.net/10400.22/13537
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationBEX 2883/15-5pt_PT
dc.relation4/02282e02286pt_PT
dc.relation6/18023-5pt_PT
dc.relationAPES-FAPEPI 08/2012pt_PT
dc.relationIF/00092/2014pt_PT
dc.relationSFRH/BD/97995/ 2013pt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0223523417306220?via%3Dihubpt_PT
dc.subjectDockingpt_PT
dc.subjectMolecular dynamics simulationspt_PT
dc.subjectMolecular mechanicspt_PT
dc.subjectPoisson-Boltzmann surface areapt_PT
dc.subjectg_mmpbsapt_PT
dc.subjectproline-Rich oligopeptidept_PT
dc.subjectToxicological predictionpt_PT
dc.titleStructure-function studies of BPP-BrachyNH 2 and synthetic analogues thereof with Angiotensin I-Converting Enzymept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F50006%2F2013/PT
oaire.citation.endPage411pt_PT
oaire.citation.startPage401pt_PT
oaire.citation.titleEuropean Journal of Medicinal Chemistrypt_PT
oaire.citation.volume139pt_PT
oaire.fundingStream5876
person.familyNameDelerue-Matos
person.givenNameCristina
person.identifier.ciencia-id9A1A-43FB-5C27
person.identifier.orcid0000-0002-3924-776X
person.identifier.ridD-4990-2013
person.identifier.scopus-author-id6603741848
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication09f6a7bd-2f15-42b0-adc5-04bd22210519
relation.isAuthorOfPublication.latestForDiscovery09f6a7bd-2f15-42b0-adc5-04bd22210519
relation.isProjectOfPublication5c06a623-3499-408c-aef9-0a1f68cb1d02
relation.isProjectOfPublication.latestForDiscovery5c06a623-3499-408c-aef9-0a1f68cb1d02

Files

Collections

ISEP – GRAQ – Artigos