Nicotianamine is a novel angiotensin-converting enzyme 2 inhibitor in soybean.
Biomed Res
; 36(3): 219-24, 2015.
Article
em En
| MEDLINE
| ID: mdl-26106051
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a carboxypeptidase which is highly homologous to angiotensin-converting enzyme (ACE). ACE2 produces vasodilator peptides angiotensin 1-7 from angiotensin II. In the present study, we synthesized various internally quenched fluorogenic (IQF) substrates (fluorophore-Xaa-Pro-quencher) based on the cleavage site of angiotensin II introducing N-terminal fluorophore N-methylanthranilic acid (Nma) and C-terminal quencher N(ε)-2,4- dinitrophenyl-lysine [Lys(Dnp)]. The synthesized mixed substrates "Nma-Xaa-Pro-Lys(Dnp)" were hydrolyzed by recombinant human (rh) ACE2. The amount of each product was determined by liquid chromatography mass spectrometry (LC-MS) with fluorescence detection and it was found that Nma-His-Pro-Lys(Dnp) is the most suitable substrate for rhACE2. The K(m), k(cat), and k(cat)/K(m) values of Nma-His-Pro-Lys(Dnp) on rhACE2 were determined to be 23.3 µM, 167 s(-1), and 7.17 µM(-1) s(-1), respectively. Using the rhACE2 and the newly developed IQF substrate, we found rhACE2 inhibitory activity in soybean and isolated the active compound soybean ACE2 inhibitor (ACE2iSB). The physicochemical data on the isolated ACE2iSB were identical to those of nicotianamine. ACE2iSB strongly inhibited rhACE2 activity with an IC50 value of 84 nM. This is the first demonstration of an ACE2 inhibitor from foodstuffs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glycine max
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Ácido Azetidinocarboxílico
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Inibidores da Enzima Conversora de Angiotensina
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Extratos Vegetais
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Peptidil Dipeptidase A
Limite:
Humans
Idioma:
En
Revista:
Biomed Res
Ano de publicação:
2015
Tipo de documento:
Article