Transcription inhibition using modified pentanucleotides

Jae Taeg Hwang, Francis E. Baltasar, Daniel L. Cole, David S. Sigman, Chi Hong B. Chen, Marc M. Greenberg

Research output: Contribution to journalArticlepeer-review


Inhibition of gene expression was recently achieved by targeting the transcriptionally competent open complex using relatively short, pentameric modified oligonucleotides at ∼60 μM. Corroborative affinity cleavage experiments using the copper complex of a phenanthroline conjugate provided the impetus to synthesize additional analogues containing substituents at the 2′-position of uridine in a derivative of 5′-GUGGA (-4 to +1), with the purpose of inhibiting transcription at lower concentrations. Conjugates of 5′-GUGGA modified at the 2′-position of uridine were convergently synthesized using a recently reported method. Seven analogues based upon the 5′-GUGGA scaffold were tested for their ability to inhibit transcription of the lac UV-5 operon. The conjugate containing a tethered pyrene showed 70% inhibition at 20 μM, and modest inhibition at as low as 5 μM. This is a significant improvement over previously tested pentanucleotides and provides direction for the preparation of a next generation of inhibitors.

Original languageEnglish (US)
Pages (from-to)2321-2328
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number10
StatePublished - May 15 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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