| Autor: |
Boschi E; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Davis S; Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States., Taylor S; Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States., Butterworth A; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Chirayath LA; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Purohit V; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Siegel LK; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Buenaventura J; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Sheriff AH; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States., Jin R; Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States., Sheardy R; Department of Chemistry & Biochemistry, Texas Woman's University , 324 Ann Stuart Science Center, P.O. Box 425859, Denton, Texas 76204-5859, United States., Yatsunyk LA; Department of Chemistry and Biochemistry, Swarthmore College , 500 College Avenue, Swarthmore, Pennsylvania 19081, United States., Azam M; Department of Chemistry, West Chester University of Pennsylvania , West Chester, Pennsylvania 19383, United States. |
| Abstrakt: |
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 dT 4 G 4 and dT 4 G 4 T 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 (dT 4 G 4 ) 4 as compared to (dT 4 G 4 T) 4 (ΔT m is 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 (K a ∼ 10 6 -10 7 μM -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. |
