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Novel dipeptidyl hydroxamic acids that inhibit human and bacterial dipeptidyl peptidase III.
Cvitesic, Ana; Sabljic, Igor; Makarevic, Janja; Abramic, Marija.
Afiliação
  • Cvitesic A; a Division of Organic Chemistry and Biochemistry , and.
  • Sabljic I; b Division of Physical Chemistry , Ruder Boskovic Institute , Bijenicka cesta 54 , Zagreb , Croatia.
  • Makarevic J; a Division of Organic Chemistry and Biochemistry , and.
  • Abramic M; a Division of Organic Chemistry and Biochemistry , and.
J Enzyme Inhib Med Chem ; 31(sup2): 40-45, 2016.
Article em En | MEDLINE | ID: mdl-27226411
Human dipeptidyl peptidase III (hDPP III), a zinc-metallopeptidase of the family M49, is an activator of the Keap1-Nrf2 cytoprotective pathway involved in defense against oxidative stress. Pathophysiological roles of DPP III have not been elucidated yet, partly due to the lack of specific inhibitors. We showed that substrate analog H-Tyr-Phe-NHOH is a strong competitive inhibitor of hDPP III, while H-Tyr-Gly-NHOH expresses much weaker inhibition. To investigate the effects of amino acid substitutions in inhibitor P1 position, we synthesized three new dipeptidyl hydroxamates and examined their influence on the activity of hDPP III and DPP III from the human gut symbiont Bacteroides thetaiotaomicron. The extent of inhibition of hDPP III, but not of bacterial enzyme, was dependent on the amino acid in P1. H-Phe-Phe-NHOH is recognized as one of the strongest inhibitors of hDPP III (Ki = 0.028 µM), and H-Phe-Leu-NHOH discriminated between human and bacterial ortholog of the M49 family.
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Proteases / Dipeptidil Peptidases e Tripeptidil Peptidases / Bacteroides thetaiotaomicron / Ácidos Hidroxâmicos Limite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de publicação: Reino Unido
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inibidores de Proteases / Dipeptidil Peptidases e Tripeptidil Peptidases / Bacteroides thetaiotaomicron / Ácidos Hidroxâmicos Limite: Humans Idioma: En Revista: J Enzyme Inhib Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de publicação: Reino Unido