Discovery and synthesis of namalide reveals a new anabaenopeptin scaffold and peptidase inhibitor.
J Med Chem
; 55(2): 735-42, 2012 Jan 26.
Article
em En
| MEDLINE
| ID: mdl-22168797
ABSTRACT
The discovery, structure elucidation, and solid-phase synthesis of namalide, a marine natural product, are described. Namalide is a cyclic tetrapeptide; its macrocycle is formed by only three amino acids, with an exocyclic ureido phenylalanine moiety at its C-terminus. The absolute configuration of namalide was established, and analogs were generated through Fmoc-based solid phase peptide synthesis. We found that only natural namalide and not its analogs containing l-Lys or l-allo-Ile inhibited carboxypeptidase A at submicromolar concentrations. In parallel, an inverse virtual screening approach aimed at identifying protein targets of namalide selected carboxypeptidase A as the third highest scoring hit. Namalide represents a new anabaenopeptin-type scaffold, and its protease inhibitory activity demonstrates that the 13-membered macrolactam can exhibit similar activity as the more common hexapeptides.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Peptídeos Cíclicos
/
Poríferos
/
Inibidores de Proteases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article