Novel short oligonucleotide conjugates as inhibitors of human telomerase

Krisztina Pongracz; Shihong Li; Brittney Shea Herbert; Ronald Pruzan; Ellen Wunder; Allison Chin; Mieczyslaw Piatyszek; Jerry Shay; Sergei M. Gryaznov

doi:10.1081/NCN-120023085

Novel short oligonucleotide conjugates as inhibitors of human telomerase

Krisztina Pongracz, Shihong Li, Brittney Shea Herbert, Ronald Pruzan, Ellen Wunder, Allison Chin, Mieczyslaw Piatyszek, Jerry Shay, Sergei M. Gryaznov

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC ₅₀ values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC ₅₀ values 100-1000-fold higher.

Original language	English (US)
Pages (from-to)	1627-1629
Number of pages	3
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	22
Issue number	5-8
DOIs	https://doi.org/10.1081/NCN-120023085
State	Published - 2003

Keywords

Oligonucleotide thio-phosphoramidates
Telomerase inhibitors

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Genetics

Access to Document

10.1081/NCN-120023085

Cite this

@article{735803b4fec341b2bc91958e46a9f1ab,

title = "Novel short oligonucleotide conjugates as inhibitors of human telomerase",

abstract = "A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC 50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC 50 values 100-1000-fold higher.",

keywords = "Oligonucleotide thio-phosphoramidates, Telomerase inhibitors",

author = "Krisztina Pongracz and Shihong Li and Herbert, {Brittney Shea} and Ronald Pruzan and Ellen Wunder and Allison Chin and Mieczyslaw Piatyszek and Jerry Shay and Gryaznov, {Sergei M.}",

year = "2003",

doi = "10.1081/NCN-120023085",

language = "English (US)",

volume = "22",

pages = "1627--1629",

journal = "Nucleosides, Nucleotides and Nucleic Acids",

issn = "1525-7770",

publisher = "Taylor and Francis Ltd.",

number = "5-8",

}

TY - JOUR

T1 - Novel short oligonucleotide conjugates as inhibitors of human telomerase

AU - Pongracz, Krisztina

AU - Li, Shihong

AU - Herbert, Brittney Shea

AU - Pruzan, Ronald

AU - Wunder, Ellen

AU - Chin, Allison

AU - Piatyszek, Mieczyslaw

AU - Shay, Jerry

AU - Gryaznov, Sergei M.

PY - 2003

Y1 - 2003

N2 - A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC 50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC 50 values 100-1000-fold higher.

AB - A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC 50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC 50 values 100-1000-fold higher.

KW - Oligonucleotide thio-phosphoramidates

KW - Telomerase inhibitors

UR - http://www.scopus.com/inward/record.url?scp=0141707878&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141707878&partnerID=8YFLogxK

U2 - 10.1081/NCN-120023085

DO - 10.1081/NCN-120023085

M3 - Article

C2 - 14565482

AN - SCOPUS:0141707878

SN - 1525-7770

VL - 22

SP - 1627

EP - 1629

JO - Nucleosides, Nucleotides and Nucleic Acids

JF - Nucleosides, Nucleotides and Nucleic Acids

IS - 5-8

ER -

Novel short oligonucleotide conjugates as inhibitors of human telomerase

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this