Probing the Hydration of the Minor Groove of A·T Synthetic DNA Polymers by Volume and Heat Changes

Luis A. Marky, Donald W. Kupke

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 ∆V accompanying binding of netropsin to these polymers, using an improved magnetic suspension densimeter. For poly-(dA)·poly(dT) we find ∆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 ∆V = −16 mL/mol of bound netrospin. 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 that 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.

Original languageEnglish (US)
Pages (from-to)9982-9988
Number of pages7
JournalBiochemistry
Volume28
Issue number26
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry

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