title: A premelting conformational transition in poly(dA)-Poly(dT) coupled to daunomycin binding.
abstract: Circular dichroism and UV absorbance spectroscopy were used to monitor and characterize a premelting conformational transition of poly(dA)-poly(dT) from one helical form to another. The transition was found to be broad, with a midpoint of tm = 29.9 degrees C and delta HVH = +19.9 kcal mol-1. The transition renders poly(dA)-poly(dT) more susceptible to digestion by DNase I and facilitates binding of the intercalator daunomycin. Dimethyl sulfoxide was found to perturb poly(dA)-poly(dT) structure in a manner similar to temperature. These combined results suggest that disruption of bound water might be linked to the observed transition. A thermodynamic analysis of daunomycin binding to poly(dA)-poly(dT) shows that antibiotic binding is coupled to the polynucleotide conformational transition. Daunomycin binding renders poly(dA)-poly(dT) more susceptible to DNase I digestion at low binding ratios, in contrast to the normal behavior of intercalators, indicating that antibiotic binding alters the conformation of the polynucleotide. The unusual thermodynamic profiles previously observed for the binding of many antibiotics to poly(dA)-poly(dT) can be explained by our results as arising from the coupling of ligand binding to the polynucleotide conformational transition. Our data further suggest a physical basis for the temperature dependence of DNA bending.
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: J E
authors.initials: JE
authors.lastname: Herrera
authors.forename: J B
authors.initials: JB
authors.lastname: Chaires
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003630:Daunorubicin / Q000378:metabolism*; D003850:Deoxyribonuclease I; D009690:Nucleic Acid Conformation; D011067:Poly dA-dT / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013816:Thermodynamics
chemical_list: D011089:Polydeoxyribonucleotides; D011067:Poly dA-dT; D003850:Deoxyribonuclease I; D003630:Daunorubicin