Study on exosite inhibitor of cathepsin K from Herba Ecliptae fractions
10.16438/j.0513-4870.2016-1234
- VernacularTitle:墨旱莲组分中组织蛋白酶K非活性位点抑制剂研究
- Author:
Yi-ping JIANG
1
;
Yan-bin WU
2
;
Lu-ping QIN
1
;
Qiao-yan ZHANG
1
;
Hai-liang XIN
1
;
Bromme DIETER
3
;
Li-ming XUE
1
Author Information
1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China
2. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
3. The University of British Columbia, Vancouver V6T1Z3, Canada
- Publication Type:ORIGINAL ARTICLES
- Keywords:
cathepsin K;
Herba Ecliptae;
active site inhibitor;
exosite inhibitor;
n-butanol fraction of Herba Ecliptae;
eclalbasaponin IX
- From:
Acta Pharmaceutica Sinica
2017;52(6):936-942
- CountryChina
- Language:Chinese
-
Abstract:
Cathepsin K (CTSK) is considered a critical pharmaceutical target in the treatment of osteoporosis. CTSK exerts proteolytic activities against regulatory proteins besides its collagenase function, which may account for some of the adverse reactions when blocked by active site-directed inhibitors. Exosite inhibitors that can discriminate between the therapeutic collagenase and other biological activities of CTSK specifically inhibit the collagenase activity of CTSK without interfering with the other proteolytic activities of the protease. Active recombinant CTSK was expressed in Pichia pastoris, and purified by n-butyl sepharose and SP sepharose column chromatography. Herba Ecliptae is a common traditional Chinese medicine in the treatment of bone diseases. Collagenase assay and benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin (Z-FR-MCA) substrate assay based on CTSK are applied to verify the exosite inhibitors. n-Butanol extract of Herba Ecliptae are the most active fraction and eclalbasaponin IX isolated from n-butanol fraction is the potential exosite inhibitor of CTSK.
