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

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

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 β-anomer of AP, the complex between (AP)6T6 and the target site G6A6·T6C6 is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 μM at pH 5.0, in contrast to 50 μM C6T6 which has no effect on the cleavage pattern. This complex is still stable at pH 6.5 producing a footprint with 1 μM oligonucleotide. Oligonucleotides containing the α-anomer of AP are much less effective than the β-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.

0305-1048
4891-4898
Cassidy, Sarah A.
2b61828b-b504-4fe4-8765-8f29f37bb110
Slickers, Peter
9120f78b-213a-4feb-ae06-19760edffbd1
Trent, John O.
aabd4141-64bf-4107-9e61-e1407c09d430
Capaldi, Daniel C.
19c9c2a3-272a-489c-ac55-a02bc3b29392
Roselt, Peter D.
381c74c6-4717-42c0-8164-f1e1ecf7ac55
Reese, Colin B.
e41dc626-93a3-4f88-9a02-a1859b136a96
Neidle, Stephen
edf2d7ee-a257-4d4c-a3ea-b3c9c42b5ff3
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f
Cassidy, Sarah A.
2b61828b-b504-4fe4-8765-8f29f37bb110
Slickers, Peter
9120f78b-213a-4feb-ae06-19760edffbd1
Trent, John O.
aabd4141-64bf-4107-9e61-e1407c09d430
Capaldi, Daniel C.
19c9c2a3-272a-489c-ac55-a02bc3b29392
Roselt, Peter D.
381c74c6-4717-42c0-8164-f1e1ecf7ac55
Reese, Colin B.
e41dc626-93a3-4f88-9a02-a1859b136a96
Neidle, Stephen
edf2d7ee-a257-4d4c-a3ea-b3c9c42b5ff3
Fox, Keith R.
9da5debc-4e45-473e-ab8c-550d1104659f

Cassidy, Sarah A., Slickers, Peter, Trent, John O., Capaldi, Daniel C., Roselt, Peter D., Reese, Colin B., Neidle, Stephen and Fox, Keith R. (1997) Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine. Nucleic Acids Research, 25 (24), 4891-4898. (doi:10.1093/nar/25.24.4891).

Record type: Article

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 β-anomer of AP, the complex between (AP)6T6 and the target site G6A6·T6C6 is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 μM at pH 5.0, in contrast to 50 μM C6T6 which has no effect on the cleavage pattern. This complex is still stable at pH 6.5 producing a footprint with 1 μM oligonucleotide. Oligonucleotides containing the α-anomer of AP are much less effective than the β-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.

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More information

Published date: 15 December 1997
Additional Information: Funding Information: This work was supported by grants from the Cancer Research Campaign (to S.N., C.B.R. and K.R.F.) and the Medical Research Council (K.R.F.).

Identifiers

Local EPrints ID: 476339
URI: http://eprints.soton.ac.uk/id/eprint/476339
ISSN: 0305-1048
PURE UUID: 48c57286-203c-4f35-b368-7d207eece8ed
ORCID for Keith R. Fox: ORCID iD orcid.org/0000-0002-2925-7315

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Date deposited: 19 Apr 2023 16:46
Last modified: 18 Mar 2024 02:32

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Contributors

Author: Sarah A. Cassidy
Author: Peter Slickers
Author: John O. Trent
Author: Daniel C. Capaldi
Author: Peter D. Roselt
Author: Colin B. Reese
Author: Stephen Neidle
Author: Keith R. Fox ORCID iD

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