New diterpene isopimara-7,15-dien-19-oic acid and its prolyl endopeptidase inhibitory activity.
ABSTRACT The ethanolic extract of the bulbs of Fritillaria imperialis was subjected to fractionation by solvent-solvent extraction. The nonpolar fraction showed inhibitory activity against prolyl endopeptidase (PEP) (EC.188.8.131.52), a large intracellular enzyme that preferentially hydrolyze proline-containing oligopeptidase at the carboxylic side of a prolyl residue. We have isolated a diterpenoid isopimara-7,15-dien-19-oic acid (1) from the nonpolar fraction of F. imperialis, and on methylation of compound 1, a methylester 2 was obtained which is a known compound previously isolated from Fritillaria thunbergii. The present article describes the isolation and structural elucidation of isopimara-7,15-dien-19-oic acid (1) by single-crystal X-ray diffraction techniques along with its prolyl endopeptidase inhibitory activity.
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ABSTRACT: Proteases have a variety of strategies for selecting substrates in order to prevent uncontrolled protein degradation. A recent crystal structure determination of prolyl oligopeptidase has suggested a way for substrate selection involving an unclosed seven-bladed beta-propeller domain. We have engineered a disulfide bond between the first and seventh blades of the propeller, which resulted in the loss of enzymatic activity. These results provided direct evidence for a novel strategy of regulation in which oscillating propeller blades act as a gating filter during catalysis, letting small peptide substrates into the active site while excluding large proteins to prevent accidental proteolysis.EMBO Reports 10/2000; 1(3):277-81. · 7.19 Impact Factor
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ABSTRACT: Two new cevanine steroidal alkaloids, impericine (1) and forticine (2) along with known bases delavine (3), persicanidine A (4), and imperialine (5) were isolated from the bulbs of Fritillaria imperialis. The structures of impericine (1) [(20R,22S,25S)-5alpha-cevanin-23-ene-3beta,6beta,16beta-triol] and forticine (2) [(20S,22S,25S)-5alpha-cevanine-3beta,6beta-diol] were determined with the help of spectroscopic studies. These steroidal bases showed anti-acetylcholinesterase and anti-butyrylcholinesterase inhibitory activity.CHEMICAL & PHARMACEUTICAL BULLETIN 09/2002; 50(8):1013-6. · 1.56 Impact Factor