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Four base recognition by triplex-forming oligonucleotides at physiological pH

Four base recognition by triplex-forming oligonucleotides at physiological pH
Four base recognition by triplex-forming oligonucleotides at physiological pH
We have achieved recognition of all 4 bp by triple helix
formation at physiological pH, using triplex-forming
oligonucleotides that contain four different synthetic
nucleotides. BAU [20-aminoethoxy-5-(3-aminoprop-1-
ynyl)uridine] recognizesATbase pairs with high affinity,
MeP (3-methyl-2 aminopyridine) binds to GC at
higher pHs than cytosine, while APP (6-(3-aminopropyl)-
7-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one)
and S [N-(4-(3-acetamidophenyl)thiazol-2-yl-acetamide)]
bind to CG and TA base pairs, respectively.
Fluorescence melting and DNase I footprinting demonstrate
successful triplex formation at a 19mer oligopurine
sequence that contains two CG and two TA
interruptions. The complexes are pH dependent, but
are still stable at pH 7.0. BAU, MeP and APP retain considerable
selectivity, and single base pair changes
opposite these residues cause a large reduction in
affinity. In contrast, S is less selective and tolerates
CG pairs as well as TA.
helix formation, selective recognition, nucleoside analogs, stable triplexes, dual recognition, dna triplexes, binding motif, duplex dna, pairs, gene
0305-1048
3025-3032
Rusling, David A.
d397afa8-d5c0-49e7-abe0-401a985278c2
Powers, Vicki E.C.
0646d625-5039-454c-a8ad-0da6bc72ae8a
Ranasinghe, Rohan T.
b29fc8b4-2a66-430a-85fa-ff1c9c261f32
Wang, Yang
7bfb9a35-82f9-4580-a448-c4fbffc7959c
Osborne, Sadie D.
9777c83c-8998-4fd6-913e-04d3902ee9cd
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Rusling, David A.
d397afa8-d5c0-49e7-abe0-401a985278c2
Powers, Vicki E.C.
0646d625-5039-454c-a8ad-0da6bc72ae8a
Ranasinghe, Rohan T.
b29fc8b4-2a66-430a-85fa-ff1c9c261f32
Wang, Yang
7bfb9a35-82f9-4580-a448-c4fbffc7959c
Osborne, Sadie D.
9777c83c-8998-4fd6-913e-04d3902ee9cd
Brown, Tom
a64aae36-bb30-42df-88a2-11be394e8c89
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f

Rusling, David A., Powers, Vicki E.C., Ranasinghe, Rohan T., Wang, Yang, Osborne, Sadie D., Brown, Tom and Fox, Keith R. (2005) Four base recognition by triplex-forming oligonucleotides at physiological pH. Nucleic Acids Research, 33 (9), 3025-3032. (doi:10.1093/nar/gki625).

Record type: Article

Abstract

We have achieved recognition of all 4 bp by triple helix
formation at physiological pH, using triplex-forming
oligonucleotides that contain four different synthetic
nucleotides. BAU [20-aminoethoxy-5-(3-aminoprop-1-
ynyl)uridine] recognizesATbase pairs with high affinity,
MeP (3-methyl-2 aminopyridine) binds to GC at
higher pHs than cytosine, while APP (6-(3-aminopropyl)-
7-methyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one)
and S [N-(4-(3-acetamidophenyl)thiazol-2-yl-acetamide)]
bind to CG and TA base pairs, respectively.
Fluorescence melting and DNase I footprinting demonstrate
successful triplex formation at a 19mer oligopurine
sequence that contains two CG and two TA
interruptions. The complexes are pH dependent, but
are still stable at pH 7.0. BAU, MeP and APP retain considerable
selectivity, and single base pair changes
opposite these residues cause a large reduction in
affinity. In contrast, S is less selective and tolerates
CG pairs as well as TA.

Full text not available from this repository.

More information

Submitted date: 6 April 2005
Published date: 23 May 2005
Keywords: helix formation, selective recognition, nucleoside analogs, stable triplexes, dual recognition, dna triplexes, binding motif, duplex dna, pairs, gene

Identifiers

Local EPrints ID: 24235
URI: https://eprints.soton.ac.uk/id/eprint/24235
ISSN: 0305-1048
PURE UUID: 31093f9c-361a-41f0-96e1-bea6780f7034
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

Catalogue record

Date deposited: 28 Mar 2006
Last modified: 06 Jun 2018 13:16

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