TITLE

Investigation and improvement of DNA cleavage models of polyamide + Cu(II) nuclease + OOH- ligands bound to DNA

AUTHOR(S)
Hongwei Yue; Yanyan Zhu; Yan Wang; Guangju Chen
PUB. DATE
January 2010
SOURCE
BMC Structural Biology;2010, Vol. 10, p35
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Copper nucleases as a famous class of artificial metallonucleases have attracted considerable interest in relation to their diverse potentials not only as therapeutic agents but also in genomic researches. Copper nucleases present high efficient oxidative cleavage of DNA, in which DNA strand scission occurs generally after hydrogen atom abstracted from a sugar moiety. In order to achieve the selective cleavage of DNA sequences by copper nucleases, the DNA specific recognition agents of the Dervan-type hairpin and cyclic polyamides can be considered as proper carriers of copper nucleases. Investigation of the DNA cleavage selectivity of copper nucleases assisted by the hairpin and cyclic polyamides at the molecular level has not yet been elucidated. Results: We carried out a series of molecular dynamics simulations for the nuclease [Cu(BPA)]2+ or [Cu(IDB)]2+ bound to the hairpin/cyclic polyamide and associated with DNA to investigate the selective DNA cleavage properties of Cu(II)-based artificial nucleases. The simulated results demonstrate that the DNA cleavage selectivity of the two nucleases assisted by the hairpin polyamide is improved efficiently. The [Cu(BPA)]2+ or [Cu(IDB)] 2+ nuclease with a substrate OOH- bound to the hairpin polyamide can be stably located at the minor groove of DNA, and possibly abstracts H atom from the sugar of DNA. However, the DNA cleavage properties of the two nucleases assisted by the cyclic polyamide are significantly poor due to the rigidity of linking region between the cyclic polyamide and nuclease. With introduction of the flexible linker -CH2CH2CH2NH2, the modified cyclic polyamide can assist the two copper nucleases to improve the selective DNA cleavage properties efficiently. Conclusion: A flexible linker and a proper binding site of the polyamide-type recognition agents play an important role in improving the DNA cleavage selectivity of copper nucleases. Current investigations provide an insight into the DNA cleavage specificities of chemical nucleases assisted by an appropriate nucleic acid recognition agent.
ACCESSION #
55570981

 

Related Articles

  • A sequence-specific threading tetra-intercalator with an extremely slow dissociation rate constant. Holman, Garen G.; Zewail-Foote, Maha; Smith, Amy Rhoden; Johnson, Kenneth A.; Iverson, Brent L. // Nature Chemistry; 

    A long-lived and sequence-specific ligand-DNA complex would make possible the modulation of biological processes for extended periods. For this purpose, we are investigating a polyintercalation approach to DNA recognition in which flexible chains of aromatic units thread back and forth...

  • Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)]4. Pagano, Bruno; Fotticchia, Iolanda; De Tito, Stefano; Mattia, Carlo A.; Mayol, Luciano; Novellino, Ettore; Randazzo, Antonio; Giancola, Concetta // Journal of Nucleic Acids;2010, p1 

    Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target...

  • Preface. Pindur, Ulf // Current Medicinal Chemistry;Apr2001, Vol. 8 Issue 5, p1l 

    Introduces a series of articles concerning analysis of DNA structure and the identification and characterization compounds that recognize and bind to any desired sequence in double-stranded DNA. Advances in sequence selective minor groove DNA effectors; Structural analysis of sequence...

  • Sequence Recognition of DNA by Lexitropsins. Goodsell, David S. // Current Medicinal Chemistry;Apr2001, Vol. 8 Issue 5, p509 

    Lexitropsins are modular polyamide molecules that are designed to read the base sequence of DNA. Lexitropsins constructed of three types of subunits-pyrrole, imidazole and hydroxypyrrole-allow full recognition of DNA base sequences. Structural studies have revealed the atomic basis of this...

  • SNP detection made simpler? DeWitt, Natalie // Nature Biotechnology;Jan2001, Vol. 19 Issue 1, p8 

    Provides an alternative for high-throughput technologies for detecting single nucleotide polymorphism (SNP) that require knowledge of sequence information. Isolation of molecules called dimeric naphthyridines that binds GG mismatches; Development of related ligands that bind to other mismatches;...

  • Improved 'Gene Chip' Analysis Promises to Speed Application of Human Genome Draft.  // Ascribe Newswire: Medicine;11/13/2001, p9 

    A small team of scientists has dramatically improved "gene chip" technology, for the first time making it a practical method for rapidly determining the sequence of genetic building blocks. The advance, likely to speed the search for disease-related genetic changes, is reported in the November...

  • DNA thermodynamic pressure: a potential contributor to genome evolution. Zimic, Mirko J.; Guerra, Daniel; Arévalo, Jorge // Transactions of the Royal Society of Tropical Medicine & Hygiene;Apr2004 Suppplement 1, Vol. 96, pS15 

    Codon usage bias is a feature of living organisms. The origin of this bias might be explained not only by external factors but also by the nature of the structure of deoxyribonucleic acid (DNA) itself. We have developed a point mutation simulation program of coding sequences, in which nucleotide...

  • Complete genomic sequence of Dracaena mottle virus, a distinct badnavirus. Yanwei Huang; Chaoqun Ji; Dickson Wang; Yun Ma; Rongxiang Fang; Xiaoying Chen // Virus Genes;Oct2007, Vol. 35 Issue 2, p423 

    Abstract  The genome of Dracaena mottle virus (DrMV) was cloned from infected Dracaena sanderiana plants, and its complete nucleotide sequence was determined and analyzed. The circular DNA genome consists of 7531 base pairs (bp) and possesses seven putative open reading frames...

  • Compressed suffix tree—a basis for genome-scale sequence analysis. Niko Välimäki; Wolfgang Gerlach; Kashyap Dixit; Veli Mäkinen // Bioinformatics;Mar2007, Vol. 23 Issue 5, p629 

    Summary: Suffix tree is one of the most fundamental data structures in string algorithms and biological sequence analysis. Unfortunately, when it comes to implementing those algorithms and applying them to real genomic sequences, often the main memory size becomes the bottleneck. This is easily...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics