Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2.
J Antibiot (Tokyo)
; 66(5): 259-64, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23340660
ABSTRACT
A 384-well microtitre plate fluorescence cleavage assay was developed to identify inhibitors of the cysteine protease falcipain-2, an important antimalarial drug target. Bioassay-guided isolation of a MeOH extract from a myxobacterium Chitinophaga sp. Y23 isolated from soil collected in Singapore, led to the identification of a new acyltetrapeptide, falcitidin (1), which displayed an IC50 value of 6 µM against falcipain-2. The planar structure of 1 was secured by NMR and MS/MS analysis. Attempts to isolate further material for biological testing were hampered by inconsistent production and by a low yield (<100 µg l(-1)). The absolute configuration of 1 was determined by Marfey's analysis and the structure was confirmed through total synthesis as isovaleric acid-D-His-L-Ile-L-Val-L-Pro-NH2. Falcitidin (1) is the first member of a new class of falcipain-2 inhibitors and, unlike other peptide-based inhibitors, does not contain reactive groups that irreversibly bind to active cysteine sites.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Inibidores de Proteases
/
Cisteína Endopeptidases
/
Antimaláricos
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Antibiot (Tokyo)
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Singapura