Inhibition of human telomerase activity by peptide nucleic acids

James C. Norton, Mieczyslaw A. Piatyszek, Woodring E. Wright, Jerry W. Shay, David R. Corey

Research output: Contribution to journalArticle

340 Scopus citations

Abstract

We report the inhibition of human telomerase activity by peptide nucleic acids (PNAs). PNAs recognize the RNA component of human telomerase (hTR) and inhibit activity of the enzyme with IC50 values in the picomolar to nanomolar range. Inhibition depends on targeting exact functional boundaries of the hTR template and is 10- to 50-fold more efficient than inhibition by analogous phosphorothioate (PS) oligomers. In contrast to high selectivity of inhibition by PNAs, PS oligomers inhibit telomerase in a nonsequence-selective fashion. These results demonstrate that PNAs can control the enzymatic activity of ribonucleoproteins and possess important advantages relative to PS oligomers in both the affinity and the specificity of their recognition. These observations should facilitate the development of effective inhibitors of telomerase activity and affinity probes of telomerase structure.

Original languageEnglish (US)
Pages (from-to)615-X3
JournalNature biotechnology
Volume14
Issue number5
DOIs
StatePublished - 1996

Keywords

  • Oligonucleotide
  • PNA
  • Phosphorothioate
  • Telomerase

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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