Sequence-dependent cooperative interactions in A/T-containing oligo- and polydeoxyribonucleotides

Abstract

To evaluate the length and sequence dependence of the unusual interaction properties observed for nonalternating A/T sequences in deoxyribonucleic acid (DNA) [Wilson, W. D., Wang, Y. H., Krishnamoorthy, C. R., & Smith, J. C. (1985) Biochemistry 24, 3991-3999], we have synthesized the oligomers d(A-T)6, dA10 X dT10, and d(A6-T6) and evaluated their interaction with the intercalator propidium. Propidium visible spectral shifts on adding all three oligomers are quite similar. Low-temperature spectrophotometric binding measurements indicate that d(A-T)6 has a significantly larger binding constant for propidium than dA10.dT10, as with the analogous alternating and nonalternating DNA polymers. The oligomer dA10.dT10 displays positive cooperativity in its propidium binding isotherm, and its binding constant increases with increasing temperature while d(A-T)6 does not display positive cooperativity, and its binding constant decreases with temperature, again as with the analogous polymers. van't Hoff plots indicate that the propidium binding enthalpies are approximately -9 and +6 kcal/mol for the alternating and nonalternating DNA samples, respectively. The mixed-sequence self-complementary oligomer d(A6-T6) has an unusual low-temperature binding isotherm which suggests a single strong binding site and a larger number of weaker binding sites which bind propidium cooperatively. A van't Hoff plot indicates that the cooperative sites d(A-T)6 have binding constants and binding enthalpies similar to dA10.dT10. Similar rate constants are observed in the sodium dodecyl sulfate driven dissociation reaction of propidium from d(A-T)6 and d(A6-T6), but the association reaction of propidium is significantly slower with d(A6-T6) than with d(A-T)6.(ABSTRACT TRUNCATED AT 250 WORDS)

Circular Dichroism Studies of the Structure of DNA Complex with Berberine

“…This is very unusual and unique, but such behaviour of this polymer towards intercalators is well documented in the literature (47)(48)(49)(50)(51). The binding of daunomycin shows unusual binding properties exhibiting positive cooperativity (47) while anomalous binding with unique features has been reported for tilorone (48), propidium (49,50), ethidium bromide (51) and acridine orange (52). The molecular basis of these observations, however, remain inconclusively described (53).…”

DNA-stacking interactions Determine the Sequence Specificity of the Deoxyribonuclease Activity of 1,10-Phenanthroline-copper Ion

“…Thermodynamic analyses of the interaction of these antibiotics with poly(dA)·poly(dT) have shown that antibiotic binding can be interpreted in terms of an allosteric transition between two conformations of the polymer that bind the antibiotic with significantly different equilibrium constants (Chaires, 1983;Wilson et al, 1985;Herrera & Chaires, 1989;Chalikian et al, 1994). The polymer conformational transition has been attributed to DNA unbending (Jones et al, 1986;Park & Breslauer, 1991;and see below). These unusual binding properties were shown to be shared by short T 6 and T 10 -tracts (Jones et al, 1986).…”

“…The polymer conformational transition has been attributed to DNA unbending (Jones et al, 1986;Park & Breslauer, 1991;and see below). These unusual binding properties were shown to be shared by short T 6 and T 10 -tracts (Jones et al, 1986). The conformational transition was characterised by a free-energy change of +1.0 to 2.0 kcal/mol in the polymer (Wilson et al, 1985;Breslauer et al, 1987) and by a transition enthalpy of +1.6 kcal/mol in the duplex d(GA 4 T 4 C) 2 (Park & Breslauer, 1991).…”

The influence of intercalator binding on DNA triplex stability: correlation with effects on A‐tract duplex structure

“…a G-C base pair) perturbs the intrinsic A-tract structure (Sandström et al, 2002;Leroy et al, 1988) and increases the thermal stability of the corresponding triplex (Sandström et al, 2002). It has been shown that intercalators bind more weakly to A-tracts than to mixed sequence duplexes, but that the binding affinity is restored to a normal level when A-tracts undergo a transition to standard B-form (Chan et al, 1990;Herrera and Chaires, 1989;Jones et al, 1986;Wilson et al, 1985). Interestingly, the intercalating drugs daunomycin and propidium are known to induce a conformational change from A-tract structure to normal B-DNA (Chan et al, 1990;Herrera and Chaires, 1989;Jones et al, 1986;Wilson et al, 1985).…”

“…It has been shown that intercalators bind more weakly to A-tracts than to mixed sequence duplexes, but that the binding affinity is restored to a normal level when A-tracts undergo a transition to standard B-form (Chan et al, 1990;Herrera and Chaires, 1989;Jones et al, 1986;Wilson et al, 1985). Interestingly, the intercalating drugs daunomycin and propidium are known to induce a conformational change from A-tract structure to normal B-DNA (Chan et al, 1990;Herrera and Chaires, 1989;Jones et al, 1986;Wilson et al, 1985). Furthermore, it has been suggested that the disruption of the A-tract structure of the underlying duplex might influence the triplex stabilizing effect of ethidium (Wilson et al, 1994;Mergny et al, 1991).…”