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

339 Citations (Scopus)

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
StatePublished - 1996

Fingerprint

Peptide Nucleic Acids
Telomerase
Human Activities
Oligomers
RNA
Ribonucleoproteins
Enzymes
Inhibitory Concentration 50

Keywords

  • Oligonucleotide
  • Phosphorothioate
  • PNA
  • Telomerase

ASJC Scopus subject areas

  • Microbiology

Cite this

Inhibition of human telomerase activity by peptide nucleic acids. / Norton, James C.; Piatyszek, Mieczyslaw A.; Wright, Woodring E.; Shay, Jerry W.; Corey, David R.

In: Nature Biotechnology, Vol. 14, No. 5, 1996, p. 615-X3.

Research output: Contribution to journalArticle

Norton, JC, Piatyszek, MA, Wright, WE, Shay, JW & Corey, DR 1996, 'Inhibition of human telomerase activity by peptide nucleic acids', Nature Biotechnology, vol. 14, no. 5, pp. 615-X3.
Norton, James C. ; Piatyszek, Mieczyslaw A. ; Wright, Woodring E. ; Shay, Jerry W. ; Corey, David R. / Inhibition of human telomerase activity by peptide nucleic acids. In: Nature Biotechnology. 1996 ; Vol. 14, No. 5. pp. 615-X3.
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