Use of ferrocene scaffolds as pendant groups in hairpin-type pyrrole-imidazole polyamide molecules showing sequence-selective binding to DNA duplexes.
[reaction: see text] The synthesis and properties of new conjugate molecules, Fc-PIA, composed of ferrocene (Fc) and pyrrole-imidazole polyamides (PIA) are reported. As a PIA sequence, we chose Im-Py-Im/Py-Im-Py considering its future application to the SNPs detection of genes having a GCG/CGC sequence. Two types of Fc-containing linkers, i.e., ferrocene-1,1'-dicarboxamide and ferrocenecarboxamide, were designed, and several Fc-PIPA molecules having these linkers were synthesized. Titration studies by use of circular dichroism revealed that the carboxamide-type Fc-PIA could bind to the target DNA with an association constant of 10(7) M(-1). In contrast, ferrocene dicarboxamide-type compounds have slightly weaker affinity for the target DNA. However, the affinity could be recovered by replacing one of the pyrrole residues with beta-alanine. We carried out the CV measurement and observed quasi-irreversible oxidation of the ferrocene moieties in the Fc-PIA compounds. These properties of Fc-PIA indicate the potential usefulness of these molecules in electrochemical detection of genes.
Seio
Kohji
K
Frontier Collaborative Research Center and Department of Life Science, Tokyo Institute of Technology, Japan Science and Technology Agency, 4259 Midori-ku, Nagatsuta-cho, Yokohama, Japan.
Mizuta
Masahiro
M
Terada
Takeshi
T
Sekine
Mitsuo
M
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005296:Ferrous Compounds / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D000075163:Metallocenes; D008968:Molecular Conformation; D009757:Nylons / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry
D005296:Ferrous Compounds; D007093:Imidazoles; D000075163:Metallocenes; D009757:Nylons; D011758:Pyrroles; C029899:imidazole; D004247:DNA; C004998:ferrocene