title: Interaction of a Cationic Porphyrin and Its Metal Derivatives with G-Quadruplex DNA.
abstract: G-quadruplex (GQ) structures formed from guanine-rich sequences are found throughout the genome and are overrepresented in the promoter regions of some oncogenes, at the telomeric ends of eukaryotic chromosomes, and at the 5'-untranslated regions of mRNA. Interaction of small molecule ligands with GQ DNA is an area of great research interest to develop novel anticancer therapeutics and GQ sensors. In this paper we examine the interactions of TMPyP4, its isomer TMPyP2 (containing N-methyl-2-pyridyl substituents, N-Me-2Py) as well as two metal derivatives ZnTMPyP4 and CuTMPyP4 with GQs formed by dT4G4and dT4G4T in 100 mM K+or Na+conditions. The DNA sequences were chosen to elucidate the effect of the 3'-T on the stabilization effect of porphyrins, binding modes, affinities, and stoichiometries determined via circular dichroism melting studies, UV-vis titrations, continuous variation analysis, and fluorescence studies. Our findings demonstrate that the stabilizing abilities of porphyrins are stronger toward (dT4G4)4as compared to (dT4G4T)4(ΔTmis 4.4 vs -6.4 for TMPyP4; 12.7 vs 5.7 for TMPyP2; 16.4 vs 12.1 for ZnTMPyP4; and 1.9 vs -8.4 °C for CuTMPyP4) suggesting that the 3'G-tetrad presents at least one of the binding sites. The binding affinity was determined to be moderate (Ka∼ 106-107μM-1) with a typical binding stoichiometry of 1:1 or 2:1 porphyrin-to-GQ. In all studies, ZnTMPyP4 emerged as a ligand superior to TMPyP4. Overall, our work contributes to clearer understanding of interactions between porphyrins and GQ DNA.
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Boschi
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States.
authors.forename: Supriya
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Taylor
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Butterworth
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Lilyan A
authors.initials: LA
authors.lastname: Chirayath
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Purohit
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Siegel
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Janesha
authors.initials: J
authors.lastname: Buenaventura
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Sheriff
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States.
authors.forename: Rowen
authors.initials: R
authors.lastname: Jin
authors.affiliation: Department of Chemistry & Biochemistry, Texas Woman's University , 324 Ann Stuart Science Center, P.O. Box 425859, Denton, Texas 76204-5859, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Sheardy
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States.
authors.forename: Liliya A
authors.initials: LA
authors.lastname: Yatsunyk
authors.affiliation: Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States.
authors.forename: Mahrukh
authors.identifier: 0000-0001-5313-5791
authors.initials: M
authors.lastname: Azam
mesh_terms: D020121:5' Untranslated Regions; D001665:Binding Sites; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008665:Metalloporphyrins / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011166:Porphyrins / Q000737:chemistry*; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry; D012996:Solutions; D013816:Thermodynamics
chemical_list: D020121:5' Untranslated Regions; D056831:Coordination Complexes; D008665:Metalloporphyrins; D011166:Porphyrins; D012996:Solutions; C568449:zinc(II) 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin; C021096:tetra(4-N-methylpyridyl)porphine; D006147:Guanine; D003300:Copper; D012964:Sodium; D011188:Potassium