title: Bcl-2 promoter sequence G-quadruplex interactions with three planar and non-planar cationic porphyrins: TMPyP4, TMPyP3, and TMPyP2.
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.
authors: Department of Chemistry, Mississippi State University, Mississippi State, Mississippi, United States of America.
authors: Vu H
authors: VH
authors: Le
authors: Narayana
authors: N
authors: Nagesh
authors: Edwin A
authors: EA
authors: Lewis
mesh_terms: D001483:Base Sequence; D002151:Calorimetry; D002412:Cations; D002942:Circular Dichroism; D054856:G-Quadruplexes; D008024:Ligands; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012996:Solutions; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013816:Thermodynamics
chemical_list: D002412:Cations; D008024:Ligands; D011166:Porphyrins; D019253:Proto-Oncogene Proteins c-bcl-2; D012996:Solutions; C021096:tetra(4-N-methylpyridyl)porphine; C107018:porphine
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