Binding of Ru(bpy)₂(eilatin)²⁺ to Matched and Mismatched DNA

Abstract

The DNA-binding properties of Ru(bpy) 2 (eilatin) 2+ have been investigated to determine if the sterically expansive eilatin ligand confers specificity for destabilized single-base mismatches in DNA. Competitive DNA photocleavage experiments employing a sequence-neutral metallointercalator, Rh(bpy) 2 (phi) 3+ (phi = 9,10-phenanthrenequinonediimine), and a mismatchspecific metalloinsertor, Rh(bpy) 2 (chrysi) 3+ (chrysi = chrysene-5,6-quinonediimine), reveal that the eilatin complex binds to a CC mismatched site with an apparent binding constant of 2.2(2) × 10 6 M −1 . Nonetheless, the selectivity in binding mismatched DNA is not high: competitive titrations with Rh(bpy) 2 (phi) 3+ show that the complex binds also to well-matched B-form sites. Thus, Ru (bpy) 2 (eilatin) 2+ , despite containing the extremely expansive eilatin ligand, displays lower selectivity for the mismatch than does Rh(bpy) 2 (chrysi) 3+ , a metalloinsertor containing the smaller, though still bulky, chrysene-5,6-quinonediimine ligand. In summary, the size and shape of the eilatin ligand allow stacking with both well-matched and mismatched DNA.

Detection of single nucleotide polymorphisms by the specific interaction between transition metal ions and mismatched base pairs in duplex DNA

“…1a) is based on the recognition of the mismatched base pairs in heteroduplex DNAs, which are newly produced by mixing, heating, and annealing two kinds of duplex DNAs with different types of SNPs [17,18]. Previously reported methods to detect the newly produced mismatched base pairs in the heteroduplex DNAs were not always convenient and accurate [19][20][21]24]. For example, the preparations of small molecules to recognize the mismatched base pairs in the heteroduplex DNA were timeconsuming for the organic synthesis of the molecules, and the small molecules did not always accurately discriminate between the target mismatched base pair and the other base pairs [19][20][21]24].…”

“…However, the need for a special gel matrix coupled with the relatively low detection rate prevented the widespread use of this approach. Additionally, some groups prepared novel small molecules to recognize mismatched base pairs in the heteroduplex DNA [19][20][21][22][23][24]. However, such preparations by organic synthesis were time-consuming, and the small molecules did not always accurately discriminate between the target mismatched base pair and the other base pairs [19][20][21]24].…”

Ruthenium polypyridyl squalene derivative: A novel self-assembling lipophilic probe for cellular imaging

“…Transition metal complexes are increasingly applied for biological applications, buttheir uptake properties have not been fully clarified (Boerner and Zaleski, 2005;Hart et al, 2006). Luminescent ruthenium complexes have been studied as oxygen sensors (Gerritsen et al, 1997) and as DNA intercalators (Zeglis and Barton, 2008). Other studies have addressed the use of Ru (II) complexes as anticancer agents (Lentz et al, 2009;Levina et al, 2009;Scolaro et al, 2005) and, more recently, as cellimaging probes.…”

Synthesis, DNA-binding, and photocleavage studies of ruthenium(II) complexes with an asymmetric ligand

“…These Ru(II) complexes have attracted considerable attention due to their rich photophysical properties and potential applications in biology, such as the design and development of non-radioactive probes of nucleic acid structure, new therapeutic reagents, synthetic restriction enzymes, versatile catalysts for divergent organic reactions, DNA foot printing agents, and possible DNA cleaving agents [1][2][3][4][5][6][7][8][9][10]. In general, Ru(II) polypyridyl complexes interact with DNA through electrostatic binding, groove binding, or intercalation.…”

“…Clarification of the trends in DNA-binding of Ru(II) polypyridyl complexes will facilitate understanding and control of interactions between the complexes and DNA, and thus mechanisms of DNA mutation and damage, as well as the design of new clinic anti-cancer drugs and complexes with biochemical activity [1][2][3][4][5].…”