title: Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates.
abstract: Bulged DNA structures are of general biological significance because of their important roles in a number of biochemical processes. Compounds capable of targeting bulged DNA sequences can be used as probes for studying their role in nucleic acid function, or could even have significant therapeutic potential. The interaction of [Fe(2)L(3)](4+) metallosupramolecular helicates (L = C(25)H(20)N(4)) with DNA duplexes containing bulges has been studied by measurement of the DNA melting temperature and gel electrophoresis. This study was aimed at exploring binding affinities of the helicates for DNA bulges of various sizes and nucleotide sequences. The studies reported herein reveal that both enantiomers of [Fe(2)L(3)](4+) bind to DNA bulges containing at least two unpaired nucleotides. In addition, these helicates show considerably enhanced affinity for duplexes containing unpaired pyrimidines in the bulge and/or pyrimidines flanking the bulge on both sides. We suggest that the bulge creates the structural motif, such as the triangular prismatic pocket formed by the unpaired bulge bases, to accommodate the [Fe(2)L(3)](4+) helicate molecule, and is probably responsible for the affinity for duplexes with a varying number of bulge bases. Our results reveal that DNA bulges represent another example of unusual DNA structures recognized by dinuclear iron(II) ([Fe(2)L(3)](4+)) supramolecular helicates.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Malina
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hannon
authors.forename: Viktor
authors.initials: V
authors.lastname: Brabec
mesh_terms: D004247:DNA / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay; D005296:Ferrous Compounds / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation
chemical_list: D005296:Ferrous Compounds; D004247:DNA
keywords: DNA melting; bulged DNA; chemical probes; metallosupramolecular helicates; unusual DNA structures