Nucleic Acids Research, 2001, Vol. 29, No. 17 3674-3684
© 2001 Oxford University Press
Synthesis and monitored selection of nucleotide surrogates for binding T:A base pairs in homopurine–homopyrimidine DNA triple helices
1Department of Chemistry, University of Constance, Fach M 709, D-78457 Konstanz, Germany and 2Department of Chemistry, Tufts University, Medford, MA 02155, USA
A total of 16 oligodeoxyribonucleotides of general sequence 5'-TCTTCTZTCTTTCT-3', where Z denotes an N-acyl-N-(2-hydroxyethyl)glycine residue, were prepared via solid phase synthesis. The ability of these oligonucleotides to form triplexes with the duplex 5'-AGAAGATAGAAAGA-HEG-TCTTTCTATCTTCT-3', where HEG is a hexaethylene glycol linker, was tested. In these triplexes, an ‘interrupting’ T:A base pair faces the Z residue in the third strand. Among the acyl moieties of Z tested, an anthraquinone carboxylic acid residue linked via a glycinyl group gave the most stable triplex, whose UV melting point was 8.4°C higher than that of the triplex with 5'-TCTTCTGTCTTTCT-3' as the third strand. The results from exploratory nuclease selection experiments suggest that a combinatorial search for strands capable of recognizing mixed sequences by triple helix formation is feasible.
* To whom correspondence should be addressed at: Department of Chemistry, University of Constance, Fach M709, D-78457 Konstanz, Germany. Tel: +49 7531 88 45 72; Fax: +49 7531 88 45 73; Email: clemens.richert{at}uni-kostanz.de Dedicated to Prof. Gerhard Schröder, Karlsruhe