Purine substrates for human thiopurine methyltransferase

Monika Deininger, Carol L. Szumlanski, Diane M. Otterness, Jon Van Loon, Wolfgang Ferber, Richard M. Weinshilboum

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). A genetic polymorphism regulating TPMT activity in human tissue is an important factor responsible for individual differences in the toxicity and therapeutic efficacy of these drugs. Because of the clinical importance of this polymorphism, we studied 18 purine derivatives, including ribonucleosides and ribonucleotides, as potential substrates for purified human kidney TPMT. Sixteen of the compounds studied were substrates for the enzyme, with Km values that varied from 29.1 to 1270 μM and with Vmax values that varied from 75 to 2340 U/mg protein. The thiopurines tested had Km values that were uniformly lower than were those of the corresponding ribonucleosides or ribonucleotides. 6-Selenopurine derivatives had the lowest Km values of the compounds studied. Finally, oxidized purines with an OH in the 8-position were methylated by the enzyme, but 2-OH compounds were potent inhibitors of TPMT.

Original languageEnglish (US)
Pages (from-to)2135-2138
Number of pages4
JournalBiochemical Pharmacology
Issue number11
StatePublished - Nov 29 1994


  • methylation
  • pharmacogenetics
  • thiopurine methyltransferase
  • thiopurines

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology


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