title: DNA tris-intercalation: first acridine trimer with DNA affinity in the range of DNA regulatory proteins. Kinetic studies.
abstract: A trimer made up of three acridine chromophores linked by a positively charged poly(aminoalkyl) chain was synthesized as a potential tris-intercalating agent. The length of the linking chain was selected to allow intercalation of each chromophore according to the excluded site model. 1H NMR studies have shown that, at 5 mM sodium, pH 5, the acridine trimer occurred under a folded conformation stabilized by stacking interactions between the three aromatic rings. DNA tris-intercalation of the dye at a low dye/base pair ratio was shown by measurements of both the unwinding of PM2 DNA and the lengthening of sonicated rodlike DNA. The trimer exhibits a high DNA affinity for poly[d(A-T)] (Kapp = 8 X 10(8) M-1, 1 M sodium) as shown by competition experiments with ethidium dimer. Kinetic studies of both the association with poly[d(A-T)] and the exchange between poly[d(A-T)] and sonicated calf thymus DNA have been performed as a function of the ionic strength. In 0.3 M sodium the on-rate constant (k1 = 2.6 X 10(7) M-1 s-1) is similar to that reported for other monoacridines or bis(acridines), whereas the off-rate constant is much smaller (k-1 = 1.2 X 10(-4) s-1), leading to an equilibrium binding constant as large as Kapp = 2.2 X 10(11) M-1. A plot of log (k1/k-1) as a function of log [Na+] yielded a straight line whose slope shows that 5.7 ion pairs (out of 7 potential) are formed upon the interaction with DNA. From this linear relationship a Kapp value of 10(14) M-1 in 0.1 M sodium can be estimated. Such a value reaches and even goes beyond that of some DNA regulatory proteins. This acridine trimer appears to be the first synthetic ligand with such a high DNA affinity.
authors.forename: P
authors.initials: P
authors.lastname: Laugâa
authors.forename: J
authors.initials: J
authors.lastname: Markovits
authors.forename: A
authors.initials: A
authors.lastname: Delbarre
authors.forename: J B
authors.initials: JB
authors.lastname: Le Pecq
authors.forename: B P
authors.initials: BP
authors.lastname: Roques
mesh_terms: D000166:Acridines / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003016:Clostridium perfringens / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008837:Micrococcus / Q000378:metabolism; D011089:Polydeoxyribonucleotides / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013950:Thymus Gland
chemical_list: D000166:Acridines; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D011089:Polydeoxyribonucleotides; D004247:DNA; C047573:acridine trimer 2; C047572:acridine trimer 1