Abstract

We have used DNase I footprinting to examine DNA triple helix formation at a 12 base pair oligopurine · oligopyrimidine sequence, using oligonucleotides that contain combinations of 2′-aminoethoxy-5-(3-aminoprop-1-ynyl)uridine (bis-amino-U, BAU) and 3-methyl-2-aminopyridine ( MeP) in place of T and C, respectively. This combination acts cooperatively to enable high affinity triple helix formation at physiological pH. The affinity depends on the number of substitutions and their arrangement; oligonucleotides in which these analogues are evenly distributed throughout the third strand bind much better than those in which they are clustered together.

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