Metal-free cleavage efficiency toward DNA by a novel PNA analog-bridged macrocyclic polyamine.

Ming-Qi Wang, Ji Zhang, Yu Zhang, Da-Wei Zhang, Qiang Liu, Jun-Liang Liu, Hong-Hui Lin, Xiao-Qi Yu

Index: Bioorg. Med. Chem. Lett. 21(19) , 5866-5869, (2011)

Full Text: HTML

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.Copyright © 2011 Elsevier Ltd. All rights reserved.