The incorporation of a platinated cross-link into duplex DNA yields an uptake of structural water

Besik I. Kankia, Donald W. Kupke, Luis A. Marky

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The anticancer activity of cisplatin arises from its ability to bind covalently to DNA, forming primarily intrastrand cross-links to adjacent guanine residues. This work is an effort to understand the hydration effects and energetics associated with the incorporation of cisplatin into duplex DNA. A combination of spectroscopy, calorimetry, density, and ultrasonic techniques was employed to investigate the unfolding (and folding) thermodynamics of a 10-mer DNA duplex with a d(GpG) platinated cross-link and its control unplatinated duplex. The platinated duplex unfolds with a lower TM value (and lower ΔG°DSC term by 3.4 kcal/mol), which results from the compensation of an unfavorable enthalpy term with a favorable entropy term. The hydration parameters at 20 °C indicated an uptake of structural water by the platinated duplex and a release of electrostricted water by the control duplex. Relative to the control duplex, the folding of the platinated duplex at 20 °C yielded a positive differential ΔG° term (and positive differential enthalpy-entropy compensation) and a negative differential volume change. The opposite signs of the ΔG° and ΔΔV terms also indicated an uptake of structural water molecules by the platinated duplex. This effect is consistent with the DNA bending and unwinding induced by the cross-link and creating a hydrophobic notch at the lesion site.

Original languageEnglish (US)
Pages (from-to)11402-11405
Number of pages4
JournalJournal of Physical Chemistry B
Volume105
Issue number46
DOIs
StatePublished - Nov 22 2001

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Fingerprint Dive into the research topics of 'The incorporation of a platinated cross-link into duplex DNA yields an uptake of structural water'. Together they form a unique fingerprint.

Cite this