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Registro Completo |
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Biblioteca(s): |
Embrapa Agricultura Digital. |
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Data corrente: |
04/08/2005 |
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Data da última atualização: |
26/01/2018 |
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Autoria: |
HERNANDEZ FERNANDEZ, J.; NESHICH, G.; CAMARGO, A. C. M. |
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Afiliação: |
JORGE HERNANDEZ FERNANDEZ, Instituto Butantan; GORAN NESHICH, CNPTIA; ANTONIO CARLOS M. CAMARGO, Instituto Butantan. |
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Título: |
Using bradykinin-potentiating peptide structures to develop new antihypertensive drugs. |
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Ano de publicação: |
2004 |
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Fonte/Imprenta: |
Genetics and Molecular Research, v. 3, n. 4, p. 554-563, 2004. |
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Idioma: |
Inglês |
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Conteúdo: |
Angiotensin I-converting enzyme (ACE) is a dipeptidyl-carboxypeptidase expressed in endothelial, epithelial and neuroepithelial cells. It is composed of two domains, known as N- and C-domains, and it is primarily involved in blood pressure regulation. Although the physiological functions of ACE are not limited to its cardiovascular role, it has been an attractive target for drug design due to its critical role in cardiovascular and renal disease. We examined natural structures based on bradykinin-potentiating peptides (BPPs) extracted from Bothrops jararaca venom for ACE inhibition. Modeling, docking and molecular dynamics were used to study the conserved residues in the S2´, S1´ and S1 positions that allow enzyme-substrate/inhibitor contacts. These positions are conserved in other oligopeptidases, and they form tight and non-specific contacts with lisinopril, enalapril and BPP9a inhibitors. The only specific inhibitor for human somatic ACE (sACE) was BPP9a, which is instable in the N-sACE-BPP9a complex due to repulsive electrostatic interactions between Arg P4-Arg 412 residues. Specificity for the C-terminal domain in human sACE inhibition was confirmed by electrostatic interaction with the Asp 1008 residue. Peptide-like BPP structures, naturally developed by snakes across millions of years of evolution, appear to be good candidates for the development of domain-selective ACE inhibitors with high stability and improved pharmacological profiles. |
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Palavras-Chave: |
Dinâmica molecular; Hipertensão; Modelagem; Modeling. |
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Thesaurus Nal: |
Hypertension; Models; Molecular dynamics. |
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Categoria do assunto: |
X Pesquisa, Tecnologia e Engenharia |
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URL: |
https://ainfo.cnptia.embrapa.br/digital/bitstream/item/171703/1/Using-bradykinin-potentiating-peptide-str.pdf
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Marc: |
LEADER 02142naa a2200229 a 4500
001 1009091
005 2018-01-26
008 2004 bl uuuu u00u1 u #d
100 1 $aHERNANDEZ FERNANDEZ, J.
245 $aUsing bradykinin-potentiating peptide structures to develop new antihypertensive drugs.$h[electronic resource]
260 $c2004
520 $aAngiotensin I-converting enzyme (ACE) is a dipeptidyl-carboxypeptidase expressed in endothelial, epithelial and neuroepithelial cells. It is composed of two domains, known as N- and C-domains, and it is primarily involved in blood pressure regulation. Although the physiological functions of ACE are not limited to its cardiovascular role, it has been an attractive target for drug design due to its critical role in cardiovascular and renal disease. We examined natural structures based on bradykinin-potentiating peptides (BPPs) extracted from Bothrops jararaca venom for ACE inhibition. Modeling, docking and molecular dynamics were used to study the conserved residues in the S2´, S1´ and S1 positions that allow enzyme-substrate/inhibitor contacts. These positions are conserved in other oligopeptidases, and they form tight and non-specific contacts with lisinopril, enalapril and BPP9a inhibitors. The only specific inhibitor for human somatic ACE (sACE) was BPP9a, which is instable in the N-sACE-BPP9a complex due to repulsive electrostatic interactions between Arg P4-Arg 412 residues. Specificity for the C-terminal domain in human sACE inhibition was confirmed by electrostatic interaction with the Asp 1008 residue. Peptide-like BPP structures, naturally developed by snakes across millions of years of evolution, appear to be good candidates for the development of domain-selective ACE inhibitors with high stability and improved pharmacological profiles.
650 $aHypertension
650 $aModels
650 $aMolecular dynamics
653 $aDinâmica molecular
653 $aHipertensão
653 $aModelagem
653 $aModeling
700 1 $aNESHICH, G.
700 1 $aCAMARGO, A. C. M.
773 $tGenetics and Molecular Research$gv. 3, n. 4, p. 554-563, 2004.
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Embrapa Agricultura Digital (CNPTIA) |
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