| Literature DB >> 20187655 |
Ching-Wen Ho1, Shinde D Popat, Ta-Wei Liu, Keng-Chang Tsai, Meng-Jung Ho, Wei-Hung Chen, An-Suei Yang, Chun-Hung Lin.
Abstract
Human N-acetyl-beta-hexosaminidase (Hex) isozymes are considered to be important targets for drug discovery. They are directly linked to osteoarthritis because Hex is the predominant glycosidase released by chondrocytes to degrade glycosaminoglycan. Hex is also associated with lysosomal storage disorders. We report the discovery of GlcNAc-type iminocyclitiols as potent and selective Hex inhibitors, likely contributed by the gain of extra electrostatic and hydrophobic interactions. The most potent inhibitor had a K(i) of 0.69 nM against human Hex B and was 2.5 x 10(5) times more selective for Hex B than for a similar human enzyme O-GlcNAcase. These glycosidase inhibitors were shown to modulate intracellular levels of glycolipids, including ganglioside-GM2 and asialoganglioside-GM2.Entities:
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Year: 2010 PMID： 20187655 DOI： 10.1021/cb100011u
Source DB: PubMed Journal: ACS Chem Biol ISSN： 1554-8929 Impact factor: 5.100