title: Metal-free cleavage efficiency toward DNA by a novel PNA analog-bridged macrocyclic polyamine.
abstract: In this report we describe the synthesis of a new class of cyclen-contained compounds with novel peptide nucleic acid (PNA) analog motif. Target bis-cyclen derivative B was prepared and characterized by ESI-MS, NMR and HPLC. Interactions between compound B and calf thymus DNA were studied by thermal denaturation. Results indicate that the DNA binding affinity of B is stronger than that of mono-cyclen compound A, and the binding ability is little affected by the change of ionic strength. Agarose and denaturing polyacrylamide gel electrophoresis were used to assess the DNA cleavage activities. The macrocyclic polyamine-PNA analog conjugate B as a nuclease model can effectively cleave DNA via an oxidative pathway at micromolar concentration (10 μM) without the use of any additional metal ions. Meanwhile, the mono-cyclen compound A shows nearly no DNA cleavage effect under the same conditions.
authors.affiliation: Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, Sichuan, PR China.
authors.forename: Ming-Qi
authors.initials: MQ
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Liu
authors.forename: Hong-Hui
authors.initials: HH
authors.lastname: Lin
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Yu
mesh_terms: D000080027:Cyclams; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D008670:Metals; D008968:Molecular Conformation; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009691:Nucleic Acid Denaturation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D010957:Plasmids; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000080027:Cyclams; D006571:Heterocyclic Compounds; D008670:Metals; D009842:Oligopeptides; D020135:Peptide Nucleic Acids; D011073:Polyamines; D017382:Reactive Oxygen Species; D004247:DNA; C038072:cyclen; D013941:Thymine