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The influence of intercalator binding on DNA triplex stability: correlation with effects on A‐tract duplex structure
Author(s) -
Sandström Karin,
Wärmländer Sebastian,
Bergman Jan,
Engqvist Robert,
Leijon Mikael,
Gräslund Astrid
Publication year - 2004
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.665
Subject(s) - duplex (building) , intercalation (chemistry) , dna , chemistry , base pair , crystallography , thermal stability , circular dichroism , triple helix , biophysics , stereochemistry , biochemistry , biology , organic chemistry
The triplex form of DNA is of interest because of a possible biological role as well as the potential therapeutic use of this structure. In this paper the stabilizing effects of two intercalating drugs, ethidium and the quinoxaline derivative 9‐OH‐B220, on DNA triplexes have been studied by thermal denaturation measurements. The corresponding duplex structures of the DNA triplex systems investigated are either A‐tract or normal B‐DNA. The largest increases in the triplex melting temperatures caused by the intercalators were found for sequences having A‐tract duplex structures. Inserting a single base pair with an N2‐amino group in the minor groove, e.g. a G–C pair, breaks up the A‐tract duplex structure and also reduces the stabilizing effect of the drugs on the triplex melting temperatures. The large drug‐induced increase in triplex melting temperature for complexes having an original duplex A‐tract structure is correlated with a low initial melting point of the triplex, not with the triplex being unusually stable in the presence of the drug. Hence, we conclude that the large thermal stabilizing effect exhibited by ethidium and 9‐OH‐B220 on d T n ·d A n –d T n triplexes is partly caused by the intercalators breaking up the intrinsic A‐tract structure of the underlying duplex. Copyright © 2004 John Wiley & Sons, Ltd.