Temperature dependence of the volumetric parameters of drug binding to poly[d(A-T)].Poly[d(A-T)] and Poly(dA).Poly(dT).
We report the temperature and salt dependence of the volume change (DeltaVb) associated with the binding of ethidium bromide and netropsin with poly(dA).poly(dT) and poly[d(A-T)].poly[d(A-T)]. The DeltaV(b) of binding of ethidium with poly(dA).poly(dT) was much more negative at temperatures approximately 70 degrees C than at 25 degrees C, whereas the difference is much smaller in the case of binding with poly[d(A-T)].poly[d(A-T)]. We also determined the volume change of DNA-drug interaction by comparing the volume change of melting of DNA duplex and DNA-drug complex. The DNA-drug complexes display helix-coil transition temperatures (Tm several degrees above those of the unbound polymers, e.g., the Tm of the netropsin complex with poly(dA)poly(dT) is 106 degrees C. The results for the binding of ethidium with poly[d(A-T)].poly[d(A-T)] were accurately described by scaled particle theory. However, this analysis did not yield results consistent with our data for ethidium binding with poly(dA).poly(dT). We hypothesize that heat-induced changes in conformation and hydration of this polymer are responsible for this behavior. The volumetric properties of poly(dA).poly(dT) become similar to those of poly[d(A-T)].poly[d(A-T)] at higher temperatures.
Shi
Xuesong
X
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada.
Macgregor
Robert B
RB
D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004996:Ethidium / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D009429:Netropsin / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011061:Poly A / Q000737:chemistry*; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D012492:Salts / Q000737:chemistry; D013696:Temperature
D011089:Polydeoxyribonucleotides; D012492:Salts; D011061:Poly A; C015465:poly(dA); D009429:Netropsin; C084838:polydeoxyadenylic acid-polythymidylic acid; D004996:Ethidium