Heterocyclic diamidine interactions at AT base Pairs in the DNA minor groove: Effects of heterocycle differences, DNA AT sequence and length

Yang Liu, Catharine J. Collar, Arvind Kumar, Chad E. Stephens, David W. Boykin, W. David Wilson

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Given the increasing significance of diamidines as DNA-targeted therapeutics and biotechnology reagents, it is important to establish the variations in thermodynamic quantities that characterize the interactions of closely related compounds to different sequence AT binding sites. In this study, an array of methods including biosensor-surface plasmon resonance (SPR), isothermal titration microcalorimetry (ITC), circular dichroism (CD), thermal melting (Tm) and molecular modeling have been used to characterize the binding of dicationic diamidines related to DB75 (amidine-phenyl-furan-phenyl-amidine) with alternating and nonalternating AT sequences. Conversion of the central furan of DB75 to other similar groups, such as thiophene or selenophene, can yield compounds with increased affinity and sequence binding selectivity for the minor groove. Calorimetric measurements revealed that the thermodynamic parameters (ΔG, ΔH, ΔS) that drive diamidine binding to alternating and nonalternating oligomers can be quite different and depend on both DNA sequence and length. Small changes in a compound can have major effects on DNA interactions. By choosing an appropriate central group it is possible to "tune" the shape of the molecule to match DNA for enhanced affinity and sequence recognition.

Original languageEnglish (US)
Pages (from-to)11809-11818
Number of pages10
JournalJournal of Physical Chemistry B
Volume112
Issue number37
DOIs
StatePublished - Sep 18 2008

Fingerprint

Pentamidine
DNA sequences
Amidines
grooves
DNA
deoxyribonucleic acid
furans
Thermodynamics
affinity
Thiophenes
Molecular modeling
Dichroism
Surface plasmon resonance
interactions
Thiophene
Binding sites
Biotechnology
Titration
Oligomers
Biosensors

ASJC Scopus subject areas

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

Cite this

Heterocyclic diamidine interactions at AT base Pairs in the DNA minor groove : Effects of heterocycle differences, DNA AT sequence and length. / Liu, Yang; Collar, Catharine J.; Kumar, Arvind; Stephens, Chad E.; Boykin, David W.; Wilson, W. David.

In: Journal of Physical Chemistry B, Vol. 112, No. 37, 18.09.2008, p. 11809-11818.

Research output: Contribution to journalArticle

Liu, Yang ; Collar, Catharine J. ; Kumar, Arvind ; Stephens, Chad E. ; Boykin, David W. ; Wilson, W. David. / Heterocyclic diamidine interactions at AT base Pairs in the DNA minor groove : Effects of heterocycle differences, DNA AT sequence and length. In: Journal of Physical Chemistry B. 2008 ; Vol. 112, No. 37. pp. 11809-11818.
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