5,10,15,20-Tetra-(N-methyl-3-pyridyl)porphyrin destabilizes the antiparallel telomeric quadruplex d(TTAGGG)4
Journal
Molecular Biology
Journal Volume
44
Journal Issue
5
Pages
823-831
Date Issued
2010
Author(s)
Abstract
5,10,15,20-Tetra-(N-methyl-3-pyridyl)porphyrin (TMPyP3) is a DNA-binding derivative of porphyrins. A comparative study of the binding of this ligand to biologically significant DNA structures was performed. For this purpose, the interactions of TMPyP3 with the antiparallel telomeric G-quadruplex d(TTAGGG)4, oligonucleotide dTTAGGGTTAGAG(TTAGGG)2 (not forming a quadruplex structure), double-stranded d(AC)8 · d(GT)8, and single-stranded d(AC)8 and d(GT)8 DNA molecules have been studied. Analysis of absorption isotherms has demonstrated that the binding constants and the number of binding sites for the complexes TMPyP3: DNA increase in the following order: d(AC)8 < d(GT)8 < d(AC)8 · d(GT)8 = d(TTAGGG)4 < dTTAGGGTTAGAG(TTAGGG)2. It has been for the first time demonstrated that the constant for TMPyP3 binding to unfolded dTTAGGGTTAGAG(TTAGGG)2 strand (1.3 × 107 M-1) is approximately threefold higher than for the G-quadruplex d(TTAGGG)4 (4.7 × 106 M-1). Binding of two TMPyP3 molecules to d(TTAGGG)4 decreases the thermostability of G-quadruplex (ΔTm = -8°C). Circular dichroism spectra of the TMPyP3 complexes with d(TTAGGG)4 suggest that the ligand partially unfolds the G-quadruplex structure. Structural destabilization of the telomeric G-quadruplex by TMPyP3 can explain the relatively low activity of this ligand as a telomerase inhibitor and a low cytotoxicity for cultured tumor cells. © 2010 Pleiades Publishing, Ltd.
Type
journal article