College of Arts and Sciences (CAS) Publications
Abstract
The interactions of three related cationic porphyrins, TMPyP4, TMPyP3 and TMPyP2, with a WT 39-mer Bcl-2 promoter sequence G-quadruplex were studied using Circular Dichroism, ESI mass spectrometry, Isothermal Titration Calorimetry, and Fluorescence spectroscopy. The planar cationic porphyrin TMPyP4 (5, 10, 15, 20-meso-tetra (N-methyl-4-pyridyl) porphine) is shown to bind to a WT Bcl-2 G-quadruplex via two different binding modes, an end binding mode and a weaker mode attributed to intercalation. The related non-planar ligands, TMPyP3 and TMPyP2, are shown to bind to the Bcl-2 G-quadruplex by a single mode. ESI mass spectrometry experiments confirmed that the saturation stoichiometry is 4:1 for the TMPyP4 complex and 2:1 for the TMPyP2 and TMPyP3 complexes. ITC experiments determined that the equilibrium constant for formation of the (TMPyP4)1/DNA complex (K1 = 3.7 ? 10(6)) is approximately two orders of magnitude greater than the equilibrium constant for the formation of the (TMPyP2)1/DNA complex, (K1 = 7.0 ? 10(4)). Porphyrin fluorescence is consistent with intercalation in the case of the (TMPyP4)3/DNA and (TMPyP4)4/DNA complexes. The non-planar shape of the TMPyP2 and TMPyP3 molecules results in both a reduced affinity for the end binding interaction and the elimination of the intercalation binding mode.
Publisher
Public Library of Science
Publication Date
8-20-2013
College
College of Arts and Sciences
Department
Department of Chemistry
Keywords
Base Sequence, Calorimetry, Cations, Circular Dichroism, Electrospray Ionization, Fluorescence, Genetic, G-Quadruplexes, Ligands, Mass, Porphyrins, Porphyrins: chemistry, Porphyrins: metabolism, Promoter Regions, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-bcl-2: genetics, Solutions, Spectrometry, Thermodynamics
Disciplines
Chemistry
Recommended Citation
Le VH, Nagesh N, Lewis EA (2013) Bcl-2 Promoter Sequence G-Quadruplex Interactions with Three Planar and Non-Planar Cationic Porphyrins: TMPyP4, TMPyP3, and TMPyP2. PLoS ONE 8(8): e72462. https://doi.org/10.1371/journal.pone.0072462
