Sequence composition effects on the stabilities of triple helix formation by oligonucleotides containing N-7-deoxyguanosine

A nonnatural nucleoside, 7-(2-deoxy-beta-D-erythropento-furanosyl)-guanine (d(7)G), mimics protonated cytosine and specifically binds GC base pairs within a pyrimidine . purine . pyrimidine triple helix. The differences in association constants (K-T) determined by quantitative footprint titration experiments at neutral pH reveal dramatic sequence composition effects on the energetics of triple helix formation by oligonucleotides containing d(7)G. Purine tracts of sequence composition 5'-d(AAAAAGAGAGAGAGA)-3' are bound by oligonucleotide 5'-d(TTTTT(7)GT(7)GT(7)GT(7)GT(7)GT)-3' three orders of magnitude less strongly than by 5'-d(TTTTT-(CTCTCTCT)-C-m-C-m-C-m-C-m)-3' (K-T = 1.5 x 10(6) M(-1) and K-T greater than or equal to 3 x 10(9) M(-1) respectively). Conversely, purine tracts of sequence composition 5'-d(AAAAGAAAAGGGGG-GA)-3' are bound by oligonucleotide 5'-d((TTTTCTT)-C-m-TT(7)G(7)G(7)G(7)G(7)G(7)GT)-3' five orders of magnitude more strongly than by 5'd((TTTCTTTTCCCCCT)-C-m-C-m-C-m-C-m-C-m-C-m)-3' (K-T greater than or equal to 3 x10(9) M(-1) and K-T < 5 x 10(4) M(-1) respectively. The complementary nature of d(7)G and C-m expands the repertoire of G-rich sequences which may be targeted by triple helix formation.