Probing the hydration of the minor groove of A.T synthetic DNA polymers by volume and heat changes.
The minor-groove ligand netropsin provides a sensitive probe of the hydration difference between poly(dA).poly(dT) and poly[d(AT)].poly[d(AT)]. We have measured the volume change delta V accompanying binding of netropsin to these polymers, using an improved magnetic suspension densimeter. For poly(dA).poly(dT) we find delta V = +97 mL/mol of bound netropsin at pH 7.0 and 10 mM sodium phosphate buffer. For poly[d(AT)].poly[d(AT)] we find delta V = -16 mL/mol of bound netropsin. This striking differential effect suggests that the poly(dA).poly(dT) duplex compresses more water (or is more extensively hydrated). From our enthalpy and entropy results we estimate the approximately 10 water molecules, immobilized in the minor groove of this system, are displaced by each netropsin bound. The volume increase, however, is substantially larger than can be explained by a simple melting of these immobilized water molecules in the minor groove. A decompression of at least 40 water molecules must attend the complexation to the poly(dA).poly(dT) duplex. This suggests that the conformation change attending the binding of the drug to this polymer duplex causes a further dehydration, whereas no such change in dehydration and configuration for the heteropolymer system is indicated.
Marky
L A
LA
Department of Chemistry, New York University, New York 10003.
Kupke
D W
DW
D001665:Binding Sites; D002151:Calorimetry; D006358:Hot Temperature; D007700:Kinetics; D009429:Netropsin / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011067:Poly dA-dT / Q000378:metabolism*; D011089:Polydeoxyribonucleotides / Q000378:metabolism*; D013816:Thermodynamics; D014867:Water / Q000378:metabolism
D011089:Polydeoxyribonucleotides; D014867:Water; D011067:Poly dA-dT; D009429:Netropsin