Role of aromacity, ring strain, and stereochemistry of selected disulfides and their congeners in the oxidative linkage of DNA strands at the major groove. A computational study

Robert Izsak, Balazs Jojart, I. Csizmadia, B. Viskolcz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Three aromatic disulfides and their two selected congeners were studied in order to see if they could be initiators or catalysts in a process that aims to tie together the two strands of a DNA double helix. Thermodynamic functions were calculated from first principle molecular computations on deoxyribose models and the disulfide congener. The gas reaction of one of the disulfides turned out to be the closest to the thermoneutral process. Solvation study caused a relatively minor energetic modification. The disulfides were subjected to docking studies, and the stabilities of the complexes obtained were further analyzed by molecular dynamics simulations. Only one of the two atropic disulfide enantiomers was the matching partner of the chiral DNA double helix, and therefore this remained in the major groove of the DNA. The other enantiomer dissociated from the major groove as it was incapable of forming a stable complex with the chiral double helix. A mechanistic scheme for the reaction has been investigated.

Original languageEnglish
Pages (from-to)2527-2536
Number of pages10
JournalJournal of Chemical Information and Modeling
Volume46
Issue number6
DOIs
Publication statusPublished - Nov 2006

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Stereochemistry
Disulfides
DNA
Enantiomers
Solvation
simulation
Molecular dynamics
Deoxyribose
Thermodynamics
Catalysts
Computer simulation
Gases

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Information Systems

Cite this

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AU - Izsak, Robert

AU - Jojart, Balazs

AU - Csizmadia, I.

AU - Viskolcz, B.

PY - 2006/11

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N2 - Three aromatic disulfides and their two selected congeners were studied in order to see if they could be initiators or catalysts in a process that aims to tie together the two strands of a DNA double helix. Thermodynamic functions were calculated from first principle molecular computations on deoxyribose models and the disulfide congener. The gas reaction of one of the disulfides turned out to be the closest to the thermoneutral process. Solvation study caused a relatively minor energetic modification. The disulfides were subjected to docking studies, and the stabilities of the complexes obtained were further analyzed by molecular dynamics simulations. Only one of the two atropic disulfide enantiomers was the matching partner of the chiral DNA double helix, and therefore this remained in the major groove of the DNA. The other enantiomer dissociated from the major groove as it was incapable of forming a stable complex with the chiral double helix. A mechanistic scheme for the reaction has been investigated.

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