Abstract
Telomerase is a ribonucleoprotein that adds 5'-d(TTAGGG)-3' hexameric repeats onto the 3' ends of chromosomes. High telomerase activity has been associated with immortal cells, transformed cells, mitogenic stimulation, and proliferative diseases. It is not clear what phenotype would be observed by transient inhibition of telomerase. Studies were designed to inhibit telomerase activity using a series of S-ODN telomere sequence motifs. The studies evaluated the length, hydrogen bonding, and sequence requirements of telomerase inhibition using the TRAP assay and a bioassay measuring cell viability following exposure to the compounds. In addition, we have also studied the role of the 3' end and secondary structure of telomere mimics on telomerase inhibition. Observations reveal that sensitivity to the S-ODNs may not require hybridization to an antisense target but required guanine nucleotides on the 3' end for cells in culture and telomerase inhibition in vitro. The importance of H bonding and the requirement for a free 3' end for the activity of these compounds has also been demonstrated. However, transient inhibition of telomerase is not cytotoxic to all immortal cells and is not sufficient to explain the mechanism of cytotoxicity of these short oligonucleotides.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 41-49 |
| Number of pages | 9 |
| Journal | Experimental Cell Research |
| Volume | 252 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 10 1999 |
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Keywords
- Drug development
- Lymphoma
- Phosphorothioate oligonucleotide
- Sarcoma
- Telomerase inhibitor
- Telomere
ASJC Scopus subject areas
- Cell Biology
Cite this
The cytotoxic effects of single-stranded telomere mimics on OMA-BL1 cells. / Page, Todd J.; Mata, John E.; Bridge, Julia A.; Siebler, Justin C; Neff, James R.; Iversen, Patrick L.
In: Experimental Cell Research, Vol. 252, No. 1, 10.10.1999, p. 41-49.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The cytotoxic effects of single-stranded telomere mimics on OMA-BL1 cells
AU - Page, Todd J.
AU - Mata, John E.
AU - Bridge, Julia A.
AU - Siebler, Justin C
AU - Neff, James R.
AU - Iversen, Patrick L.
PY - 1999/10/10
Y1 - 1999/10/10
N2 - Telomerase is a ribonucleoprotein that adds 5'-d(TTAGGG)-3' hexameric repeats onto the 3' ends of chromosomes. High telomerase activity has been associated with immortal cells, transformed cells, mitogenic stimulation, and proliferative diseases. It is not clear what phenotype would be observed by transient inhibition of telomerase. Studies were designed to inhibit telomerase activity using a series of S-ODN telomere sequence motifs. The studies evaluated the length, hydrogen bonding, and sequence requirements of telomerase inhibition using the TRAP assay and a bioassay measuring cell viability following exposure to the compounds. In addition, we have also studied the role of the 3' end and secondary structure of telomere mimics on telomerase inhibition. Observations reveal that sensitivity to the S-ODNs may not require hybridization to an antisense target but required guanine nucleotides on the 3' end for cells in culture and telomerase inhibition in vitro. The importance of H bonding and the requirement for a free 3' end for the activity of these compounds has also been demonstrated. However, transient inhibition of telomerase is not cytotoxic to all immortal cells and is not sufficient to explain the mechanism of cytotoxicity of these short oligonucleotides.
AB - Telomerase is a ribonucleoprotein that adds 5'-d(TTAGGG)-3' hexameric repeats onto the 3' ends of chromosomes. High telomerase activity has been associated with immortal cells, transformed cells, mitogenic stimulation, and proliferative diseases. It is not clear what phenotype would be observed by transient inhibition of telomerase. Studies were designed to inhibit telomerase activity using a series of S-ODN telomere sequence motifs. The studies evaluated the length, hydrogen bonding, and sequence requirements of telomerase inhibition using the TRAP assay and a bioassay measuring cell viability following exposure to the compounds. In addition, we have also studied the role of the 3' end and secondary structure of telomere mimics on telomerase inhibition. Observations reveal that sensitivity to the S-ODNs may not require hybridization to an antisense target but required guanine nucleotides on the 3' end for cells in culture and telomerase inhibition in vitro. The importance of H bonding and the requirement for a free 3' end for the activity of these compounds has also been demonstrated. However, transient inhibition of telomerase is not cytotoxic to all immortal cells and is not sufficient to explain the mechanism of cytotoxicity of these short oligonucleotides.
KW - Drug development
KW - Lymphoma
KW - Phosphorothioate oligonucleotide
KW - Sarcoma
KW - Telomerase inhibitor
KW - Telomere
UR - http://www.scopus.com/inward/record.url?scp=0033544006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033544006&partnerID=8YFLogxK
U2 - 10.1006/excr.1999.4613
DO - 10.1006/excr.1999.4613
M3 - Article
C2 - 10502398
AN - SCOPUS:0033544006
VL - 252
SP - 41
EP - 49
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -