title: Specific recognition and stabilization of monomeric and multimeric G-quadruplexes by cationic porphyrin TMPipEOPP under molecular crowding conditions.
abstract: Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ≈ 200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditions and introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.
authors: Department of Chemistry, Tianjin University, Tianjin 300072, PR China. zhu@tju.edu.cn
authors: Li-Na
authors: LN
authors: Zhu
authors: Bin
authors: B
authors: Wu
authors: De-Ming
authors: DM
authors: Kong
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry; D054856:G-Quadruplexes; D010880:Piperidines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011166:Porphyrins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D016615:Telomere / Q000737:chemistry
chemical_list: C576800:5,10,15,20-tetra-(4-(2-(1-methyl-1- piperidinyl)ethoxy)phenyl)porphyrin; D004277:DNA, Single-Stranded; D010880:Piperidines; D011166:Porphyrins; C051802:triplex DNA; D011092:Polyethylene Glycols; D004247:DNA