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Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine.

Cassidy, SA; Slickers, P; Trent, JO; Capaldi, DC; Roselt, PD; Reese, CB; Neidle, S; (1997) Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine. Nucleic Acids Res , 25 (24) 4891 - 4898. 10.1093/nar/25.24.4891. Green open access

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Abstract

We have attempted to alleviate the pH dependency of triplex recognition of guanine by using intermolecular triplexes containing 2-amino-5-(2-deoxy-d-ribofuranosyl)pyridine (AP) as an analogue of 2'-deoxycytidine (dC). We find that for the beta-anomer of AP, the complex between (AP)6T6and the target site G6A6*T6C6is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 microM at pH 5.0, in contrast to 50 microM C6T6which has no effect on the cleavage pattern. This complex is still stable at pH 6.5 producing a footprint with 1 microM oligonucleotide. Oligonucleotides containing the alpha-anomer of AP are much less effective than the beta-anomer, though in some instances they are more stable than the unmodified oligonucleotides. The results of molecular dynamics studies on a range of AP-containing triplexes has rationalized the observed stability behaviour in terms of hydrogen-bonding behaviour.

Type: Article
Title: Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine.
Location: ENGLAND
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/nar/25.24.4891
Publisher version: http://dx.doi.org/10.1093/nar/25.24.4891
Language: English
Additional information: PMCID: PMC147136. © 1997 Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: 5-Methylcytosine, Aminopyridines, Base Composition, Cytosine, DNA Footprinting, Hydrogen Bonding, Hydrogen-Ion Concentration, Models, Molecular, Nucleic Acid Conformation, Oligonucleotides, Polydeoxyribonucleotides, Substrate Specificity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/1367896
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