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 language | English (US) |
|---|---|
| Pages (from-to) | 615-X3 |
| Journal | Nature Biotechnology |
| Volume | 14 |
| Issue number | 5 |
| State | Published - 1996 |
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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 journal › Article
}
TY - JOUR
T1 - Inhibition of human telomerase activity by peptide nucleic acids
AU - Norton, James C.
AU - Piatyszek, Mieczyslaw A.
AU - Wright, Woodring E.
AU - Shay, Jerry W.
AU - Corey, David R.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - Oligonucleotide
KW - Phosphorothioate
KW - PNA
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=0029867408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029867408&partnerID=8YFLogxK
M3 - Article
VL - 14
SP - 615-X3
JO - Biotechnology
JF - Biotechnology
SN - 0733-222X
IS - 5
ER -