Sulfated chitooligosaccharides as prolyl endopeptidase inhibitor.
Prolyl endopeptidase (PEP, EC 3.4.21.26) is a proline-specific endopeptidase with a serine-type mechanism, which digests small peptide-like hormones, neuroactive peptides, and various cellular factors. PEP has been involved in neurodegenerative disorders, therefore, the discovery of PEP inhibitors can revert memory loss caused by amnesic compounds. In this study, we prepared hetero-chitooligosaccharides (COSs) with different molecular sizes using ultrafiltration (UF) membrane reactor system from hetero-chitosan with different degrees of deacetylation (DD; 90%, 75% and 50% deacetylation), and synthesized sulfated COSs (SCOSs). PEP inhibitory activities of SCOSs were evaluated and the results showed that 50% deacetylated SCOSs (50-SCOSs) exhibited higher inhibitory activities than those of 90% and 75% deacetylated SCOSs (90-SCOSs and 75-SCOSs). Among the 50-SCOSs (50-SCOS I, 5000-10,000Da; 50-SCOS II, 1000-5000Da; 50-SCOS III, below 1000Da), 50-SCOS II possessed the highest inhibitory activity and IC(50) value was 0.38mg/ml. Kinetics studies with 50-SCOS II indicated a competitive enzyme inhibition with a K(i) value of 0.78mg/ml. It was concluded that the 50-SCOS II may be useful for PEP inhibitor and for developing a new type PEP inhibitor from carbohydrate based materials.
Je
Jae-Young
JY
Division of Food Science and Aqualife Medicine, Chonnam National University, Yosu 550-749, Republic of Korea.
Kim
Eun-Kyung
EK
Ahn
Chang-Bum
CB
Moon
Sang-Ho
SH
Jeon
Byong-Tae
BT
Kim
Bokyung
B
Park
Tae-Kyu
TK
Park
Pyo-Jam
PJ
D048271:Chitosan / Q000494:pharmacology*; D007700:Kinetics; D009844:Oligosaccharides / Q000494:pharmacology*; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013464:Sulfuric Acids / Q000494:pharmacology
D009844:Oligosaccharides; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D013464:Sulfuric Acids; D048271:Chitosan; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases