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Activation and inhibition of the proteasome by betulinic acid and its derivatives
Author(s) -
Huang Li,
Ho Phong,
Chen Chin-Ho
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.09.031
Subject(s) - proteasome , betulinic acid , chemistry , activator (genetics) , biochemistry , side chain , catabolism , enzyme , stereochemistry , biology , organic chemistry , polymer , genetics , gene
This study discovered that betulinic acid (BA) is a potent proteasome activator that preferentially activates the chymotrypsin‐like activity of the proteasome. Chemical modifications can transform BA into proteasome inhibitors. Chemical modifications at the C‐3 position of BA resulted in compounds, such as dimethylsuccinyl BA (DSB), with various inhibitory activities against the human 20S proteasome. Interestingly, the proteasomal activation by BA and the inhibitory activity of DSB could be abrogated by introducing a side chain at the C‐28 position. In summary, this study discovered a class of small molecules that can either activate or inhibit human proteasome activity depending on side chain modifications.