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Selectivity and affinity of triplex-forming oligonucleotides containing 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine for recognizing AT base pairs in duplex DNA

Selectivity and affinity of triplex-forming oligonucleotides containing 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine for recognizing AT base pairs in duplex DNA
Selectivity and affinity of triplex-forming oligonucleotides containing 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine for recognizing AT base pairs in duplex DNA
We have used DNase I footprinting, fluorescence and ultraviolet (UV) melting experiments and circular dichroism to demonstrate that, in the parallel triplex binding motif, 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine (bis-amino-U, BAU) has very high affinity for AT relative to all other Watson-Crick base pairs in DNA. Complexes containing two or more substitutions with this nucleotide analogue are stable at pH 7.0, even though they contain several C.GC base triplets. These modified triplex-forming oligonucleotides retain exquisite sequence specificity, with enhanced discrimination against YR base pairs (especially CG). These properties make BAU a useful base analogue for the sequence-specific creation of stable triple helices at pH 7.0.
double-stranded dna, c+center-dot-gc, helix formation, -aminoethoxy-modified oligonucleotides, dual recognition, gene-expression, stability, stabilization, spectroscopy, polyamines
0305-1048
4439-4447
Osborne, Sadie D.
9777c83c-8998-4fd6-913e-04d3902ee9cd
Powers, Vicki E.C.
0646d625-5039-454c-a8ad-0da6bc72ae8a
Rusling, David A.
d397afa8-d5c0-49e7-abe0-401a985278c2
Lack, Oliver
cfbb55aa-1dbb-4088-bb67-0d58f7aa07a0
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Osborne, Sadie D.
9777c83c-8998-4fd6-913e-04d3902ee9cd
Powers, Vicki E.C.
0646d625-5039-454c-a8ad-0da6bc72ae8a
Rusling, David A.
d397afa8-d5c0-49e7-abe0-401a985278c2
Lack, Oliver
cfbb55aa-1dbb-4088-bb67-0d58f7aa07a0
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89

Osborne, Sadie D., Powers, Vicki E.C., Rusling, David A., Lack, Oliver, Fox, Keith R. and Brown, Tom (2004) Selectivity and affinity of triplex-forming oligonucleotides containing 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine for recognizing AT base pairs in duplex DNA. Nucleic Acids Research, 32 (15), 4439-4447. (doi:10.1093/nar/gkh776).

Record type: Article

Abstract

We have used DNase I footprinting, fluorescence and ultraviolet (UV) melting experiments and circular dichroism to demonstrate that, in the parallel triplex binding motif, 2'-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine (bis-amino-U, BAU) has very high affinity for AT relative to all other Watson-Crick base pairs in DNA. Complexes containing two or more substitutions with this nucleotide analogue are stable at pH 7.0, even though they contain several C.GC base triplets. These modified triplex-forming oligonucleotides retain exquisite sequence specificity, with enhanced discrimination against YR base pairs (especially CG). These properties make BAU a useful base analogue for the sequence-specific creation of stable triple helices at pH 7.0.

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More information

Published date: 2004
Keywords: double-stranded dna, c+center-dot-gc, helix formation, -aminoethoxy-modified oligonucleotides, dual recognition, gene-expression, stability, stabilization, spectroscopy, polyamines

Identifiers

Local EPrints ID: 20299
URI: http://eprints.soton.ac.uk/id/eprint/20299
ISSN: 0305-1048
PURE UUID: ce5948f3-4763-4b03-94a8-3efeded97fee
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

Catalogue record

Date deposited: 20 Feb 2006
Last modified: 16 Mar 2024 02:36

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Contributors

Author: Sadie D. Osborne
Author: Vicki E.C. Powers
Author: David A. Rusling
Author: Oliver Lack
Author: Keith R. Fox ORCID iD
Author: Tom Brown

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