Evidence map›Paper›PMID 20701359›Full record

ArticleBiochemistry2010

Targeting of an interrupted polypurine:polypyrimidine sequence in mammalian cells by a triplex-forming oligonucleotide containing a novel base analogue.

A Semenyuk, E Darian, J Liu, A Majumdar, B Cuenoud, P S Miller, A D Mackerell, M M Seidman

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 70 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

A SemenyukNational Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
E Darian
J Liu
A Majumdar
B Cuenoud
P S Miller
A D Mackerell
M M Seidman
National Institute on Aging · USUniversity of Maryland, Baltimore · USJohns Hopkins University · USMerck Serono (Switzerland) · CHNational Institutes of Health · US

Funding

Oligonucleotide Conformational HeterogeneityR01GM051501 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI MACKERELL, ALEXANDER D · 2003 to 2018
$3.6M
Gene Targeting Mediated By Triple Helix Forming OligonucleotidesZ01AG000738 · NIA · NATIONAL INSTITUTE ON AGING · PI SEIDMAN, MICHAEL M · 1999 to 2008
$1.4M
Repair of localized DNA damageZ01AG000746 · NIA · NATIONAL INSTITUTE ON AGING · PI SEIDMAN, MICHAEL · 2007 to 2008
$607k
Gene Targeting Mediated By Triple Helix Forming OligonucleotidesZIAAG000738 · NIA · NATIONAL INSTITUTE ON AGING · PI SEIDMAN, MICHAEL · 2009 to 2010
$144k
HALOGEN FREE ENERGY DATABASE FOR RATIONAL DRUG DESIGNR29GM051501 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI MACKERELL, ALEXANDER D. · 1996 to 2000
$108k
Intramural NIH HHS Z01 AG000738Intramural NIH HHS Z01 AG000746NIA NIH HHS Z01 AG000746-10NIGMS NIH HHS GM051501NIGMS NIH HHS R01 GM051501NIGMS NIH HHS R29 GM051501
6 · The paper itself

Abstract

The DNA triple helix consists of a third strand of nucleic acid lying in the major groove of an intact DNA duplex. The most stable triplexes form on polypurine:polypyrimidine sequences, and pyrimidine interruptions in the purine strand are destabilizing. Sequence stringency is imparted by specific Hoogsteen hydrogen bonds between third strand bases and the purine bases in the duplex. Appropriate base and sugar modifications of triple helix-forming oligonucleotides (TFOs) confer chromosome targeting activity in living cells. However, broad utilization of TFOs as gene targeting reagents in mammalian cells has been limited by the requirement for homopurine target sequences. Although there have been a number of base analogues described that appear to be promising as candidates for triplex target expansion, none has been examined in a biological system. We have employed a postsynthetic strategy to prepare a collection of TFOs with base analogues at a defined position. Following assessment of affinity for a triplex target with a single C:G inversion, TFOs with a second generation of analogues were synthesized. One of these, TFO-5a, with 2'-OMe-guanidinylethyl-5-methylcytosine at the position corresponding to the C:G interruption in the target sequence, was further modified to confer bioactivity. The activity of this TFO, linked to psoralen, was measured in a mammalian cell line that was engineered by directed sequence conversion to carry a triplex target with a single C:G interruption. TFO-5a was active against this target and inactive against the corresponding target with an uninterrupted polypurine:polypyrimidine sequence.

Indexed as

AnimalsBase SequenceCHO CellsCricetinaeCricetulusDNAHumansNucleic Acid ConformationOligonucleotidesPurinesPyrimidinesDNAOligonucleotidesPurinesPyrimidinestriplex DNA

Identifiers

PMID20701359
PMCPMC2935506
OpenAlexW2033965361

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.