BINDING AFFINITIES OF SYNTHETIC PEPTIDES, PYRIDINE-2-CARBOXAMIDONETROPSIN AND 1-METHYLIMIDAZOLE-2-CARBOXAMIDONETROPSIN, THAT FORM 2 1 COMPLEXES IN THE MINOR-GROOVE OF DOUBLE-HELICAL DNA/
Ws. Wade et al., BINDING AFFINITIES OF SYNTHETIC PEPTIDES, PYRIDINE-2-CARBOXAMIDONETROPSIN AND 1-METHYLIMIDAZOLE-2-CARBOXAMIDONETROPSIN, THAT FORM 2 1 COMPLEXES IN THE MINOR-GROOVE OF DOUBLE-HELICAL DNA/, Biochemistry, 32(42), 1993, pp. 11385-11389
The designed peptides pyridine-2-carboxamidonetropsin (2-PyN) and 1-me
thylimidazole-2-caboxamidonetropsin (2-ImN) are crescent-shaped analog
s of the natural products netropsin and distamycin A. 2-PyN and 2-ImN
bind the 5'-TGTCA-3' sequence as antiparallel side-by-side dimers in t
he minor groove of DNA. The binding affinities of 2-PyN and 2-ImN to f
our different 5-bp sites on DNA were determined by quantitative MPE.Fe
(II) footprint titration and compared with the tripeptide D from dista
mycin. The binding affinities of D to the sites 5'-TTTTT-3' and 5'-TGT
CA-3' are 2.6 x 10(7) and < 1 x 10(5) M-1, respectively (pH 7.0, 100 m
M NaCl). 2-PyN binds these sites with similar affinities, 2.3 x 10(5)
and 2.7 x 10(5) M-1, respectively. The affinities of 2-ImN to the same
two sites are <5 x 10(4) and 1.4 x 10(5) M-1, respectively. Substitut
ion of an N-methylpyrrole-2-carboxamide of the distamycin tripeptide b
y 1-methylimidazole-2-carboxamide has changed the specificities for th
e two binding sites by a factor of 10(3). The data for 2-PyN and 2-ImN
binding the 5'-TGTCA-3' site are best fit by a cooperative binding cu
rve consistent with 2:1 peptide-DNA complexes.