Effect of chemical modification of oligohomopyrimidine on triplex formation: thermodynamic and kinetic studies.
To investigate the effect of chemical modification of the third strand on the stability of triplex DNA, we have examined the thermodynamic properties of the triplex formation between a 23-mer double-stranded homopurine-homopyrimidine and each of five kinds of 15-mer chemically modified single-stranded homopyrimidines by isothermal titration calorimetry, and the kinetic properties by interaction analysis system. The modifications of the third strand included two base modifications, two sugar moiety modifications, and one phosphate backbone modification. The thermodynamic and kinetic parameters for the triplex formation were similar in magnitude among the two base-modified and two sugar-modified single strands. By contrast, the binding constant for the triplex formation with the single strand with phosphorothioate backbone was more than ten times as small as that for the other triplex formation. On the basis of the kinetic analyses, the single strand with phosphorothioate backbone was more difficult to associate with and easier to dissociate from the target double strand than the other single strands, which resulted in the much smaller binding constant.
Torigoe
H
H
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Shimizume
R
R
Sarai
A
A
Shindo
H
H
D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry; D007700:Kinetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011742:Pyrimidine Nucleotides; D013816:Thermodynamics
D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D011742:Pyrimidine Nucleotides; D004247:DNA