Controlling Sulfuryl-Transfer Biology

Ian Cook, Ting Wang, Wei Wang, Felix Kopp, Peng Wu, Thomas S. Leyh

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Summary In humans, the cytosolic sulfotransferases (SULTs) catalyze regiospecific transfer of the sulfuryl moiety (-SO3) from 3′-phosphoadenosine 5′-phosphosulfate to thousands of metabolites, including numerous signaling small molecules, and thus regulates their activities and half-lives. Imbalances in the in vivo set points of these reactions leads to disease. Here, with the goal of controlling sulfonation in vivo, molecular ligand-recognition principles in the SULT and nuclear receptor families are integrated in creating a strategy that can prevent sulfonation of a compound without significantly altering its receptor affinity, or inhibiting SULTS. The strategy is validated by using it to control the sulfonation and estrogen receptor (ER) activating activity of raloxifene (a US Food and Drug Administration-approved selective estrogen receptor modulator) and its derivatives. Preventing sulfonation is shown to enhance ER-activation efficacy 104-fold in studies using Ishikawa cells. The strategy offers the opportunity to control sulfuryl transfer on a compound-by-compound basis, to enhance the efficacy of sulfonated drugs, and to explore the biology of sulfuryl transfer with unprecedented precision.

Original languageEnglish (US)
Pages (from-to)579-586
Number of pages8
JournalCell Chemical Biology
Issue number5
StatePublished - May 19 2016


  • derivatives
  • estrogen receptor
  • inhibition
  • mechanism
  • raloxifene
  • selectivity
  • structure
  • sulfation
  • sulfonation
  • sulfotransferase
  • synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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