title: Two cationic porphyrin isomers showing different multimeric G-quadruplex recognition specificity against monomeric G-quadruplexes.
abstract: Ligands that can interact specifically with telomeric multimeric G-quadruplexes could be developed as promising anticancer drugs with few side effects related to other G-quadruplex-forming regions. In this paper, a new cationic porphyrin derivative, m-TMPipEOPP, was synthesized and characterized. Its multimeric G-quadruplex recognition specificity under molecular crowding conditions was compared to its isomer p-TMPipEOPP. The slight structural difference accounts for different multimeric G-quadruplex recognition specificity for the two isomers. p-TMPipEOPP can barely discriminate between multimeric and monomeric G-quadruplexes. By contrast, m-TMPipEOPP can bind with multimeric but not with monomeric G-quadruplexes. p-TMPipEOPP might bind to multimeric G-quadruplexes by two modes: sandwich-like end-stacking mode and pocket-dependent intercalative mode. Increasing the pocket size between adjacent two G-quadruplex units is beneficial for the latter mode. m-TMPipEOPP might bind to multimeric G-quadruplexes by a side binding mode, which confers m-TMPipEOPP with higher multimeric G-quadruplex recognition specificity compared to p-TMPipEOPP. m-TMPipEOPP increases the stability of multimeric G-quadruplex under both dilute and molecular crowding conditions but its G-quadruplex-stabilizing ability is a little weaker than p-TMPipEOPP. These results provide important information for the design of highly specific multimeric G-quadruplex ligands. Another interesting finding is that pocket size is an important factor in determining the stability of multimeric G-quadruplexes.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, PR China Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Huang
authors.affiliation: Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China Department of Chemistry, Tianjin University, Tianjin 300072, PR China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, Tianjin University, Tianjin 300072, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Tianjin University, Tianjin 300072, PR China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Huo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, PR China Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, PR China Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, PR China kongdem@nankai.edu.cn.
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Kong
mesh_terms: D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D005453:Fluorescence; D054856:G-Quadruplexes; D007536:Isomerism; D010880:Piperidines; D011166:Porphyrins / 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; D004247:DNA