Structure-based design, synthesis, and biological evaluation of Leu-Arg dipeptide analogs as novel hepsin inhibitors.
Bioorg Med Chem Lett
; 26(2): 310-314, 2016 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-26711145
ABSTRACT
Hepsin, a type II transmembrane serine protease, is an attractive protein as a potential therapeutic and diagnostic biomarker for prostate cancer because it is highly up-regulated in prostate cancer and promotes both progression and metastasis. Starting from the reported tetrapeptide hepsin inhibitor Ac-KQLR-ketothiazole (kt) (1), we investigated the minimal structural requirements for hepsin inhibitory activity by truncating amino acids at the N-terminus. The kt and ketobenzothiazole (kbt) dipeptide analogs Ac-LR-kt (3) and Ac-LR-kbt (15) were found to be potent hepsin inhibitors, exhibiting Ki values of 22nM and 3nM, respectively. The present work suggests that LR-containing dipeptide molecules could be useful as lead compounds for the development of novel hepsin inhibitors.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tiazoles
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Serina Endopeptidasas
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Inhibidores de Serina Proteinasa
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Dipéptidos
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Benzotiazoles
Límite:
Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article