S. White et al., ORIENTATION PREFERENCES OF PYRROLE-IMIDAZOLE POLYAMIDES IN THE MINOR-GROOVE OF DNA, Journal of the American Chemical Society, 119(38), 1997, pp. 8756-8765
In order to determine whether there is an orientation preference of py
rrole-imidazole (Py-lm) polyamide dimers with respect to the 5'-3' dir
ection of the backbone in the DNA helix, equilibrium association const
ants (K-a) were determined for a series of six-ring hairpin polyamides
which differ with respect to substitution at the N and C termini. Aff
inity cleaving experiments using hairpin polyamides of core sequence c
omposition ImPyPy-gamma-PyPyPy with an EDTA . Fe(II) moiety at the C-t
erminus reveal a single binding orientation at each formal match site,
5'-(A,T)G(A,T)(3)-3' and 5'-(A,T)C(A,T)(3)-3'. A positive charge at t
he C-terminus and no substitution at the N-terminus imidazole affords
the maximum binding orientation preference, calculated from K-a(5'-TGT
TA-3')/K-a(5'-TCTTA-3'), with the N-terminal end of each three-ring su
bunit located toward the 5' side of the target DNA strand. Removal of
the positive charge, rearrangement of the positive charge to the N-ter
minus or substitution at the N-terminal imidazole decreases the orient
ation preference. These results suggest that second generation design
principles superimposed on the simple pairing rules can further optimi
ze the sequence-specificity of Py-Im polyamides for double helical DNA
.