Oligonucleotide transition state analogues of saporin L3

Jennifer M. Mason, Hongling Yuan, Gary B. Evans, Peter C. Tyler, Quan Du, Vern L. Schramm

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Ribosome inactivating proteins (RIPs) are among the most toxic agents known. More than a dozen clinical trials against refractory cancers have been initiated using modified RIPs with impressive results. However, dose-limiting toxicity due to vascular leak syndrome limits success of the therapy. We have previously reported some tight-binding transition state analogues of Saporin L3 that mimic small oligonucleotide substrates in which the susceptible adenosine has been replaced by a 9-deazaadenyl hydroxypyrrolidinol derivative. They provide the first step in the development of rescue agents to prevent Saporin L3 toxicity on non-targeted cells. Here we report the synthesis, using solution phase chemistry, of these and a larger group of transition state analogues. They were tested for inhibition against Saporin L3 giving Kivalues as low as 3.3 nM and indicating the structural requirements for inhibition.

Original languageEnglish (US)
Pages (from-to)793-809
Number of pages17
JournalEuropean Journal of Medicinal Chemistry
StatePublished - 2017


  • Aza-sugar
  • Oligonucleotide
  • Ribosome inactivating protein
  • Saporin
  • Transition state inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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