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Triptolide directly inhibits dCTP pyrophosphatase.


ABSTRACT: 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.

SUBMITTER: Corson TW 

PROVIDER: S-EPMC3503517 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Triptolide directly inhibits dCTP pyrophosphatase.

Corson Timothy W TW   Cavga Hüseyin H   Aberle Nicholas N   Crews Craig M CM  

Chembiochem : a European journal of chemical biology 20110610 11


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  ...[more]

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