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

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).

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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Contributors

Author: Keith R. Fox

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