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Triptolide Directly Inhibits dCTP Pyrophosphatase
Author(s) -
Corson Timothy W.,
Cavga Hüseyin,
Aberle Nicholas,
Crews Craig M.
Publication year - 2011
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100007
Subject(s) - triptolide , pyrophosphatase , chemistry , biochemistry , inorganic pyrophosphatase , microbiology and biotechnology , biophysics , enzyme , biology , apoptosis , pyrophosphate
Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti‐inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide‐interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide.