These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: DNA hydrolytic cleavage catalyzed by synthetic multinuclear metallonucleases.
    Author: Liu C, Wang L.
    Journal: Dalton Trans; 2009 Jan 14; (2):227-39. PubMed ID: 19089001.
    Abstract:
    Much effort has been directed at understanding the roles of metal ions in catalyzing the hydrolysis of phosphodiester bonds of nucleic acids. Nucleases are metalloenzymes that have a wide variety of active site motifs and that contain a variety of different metal ions. This property has made it difficult to propose a simple mechanism for these enzymes. Therefore, design and synthesis of metal complexes, which can mediate phosphodiester bond cleavage via hydrolytic pathways, are of important significance in elucidation of the catalytic mechanisms for the natural nucleases and in development of the biomacromolecule-targeted drugs. Recent progress has extended to the design of synthetic multinuclear metallonucleases containing two or more Fe(III), Zn(II), Cu(II), Co(II/III), or Ln(III/IV) ions. The ligands in these complexes include natural and nonnatural organic molecules, i.e., mainly benzimidazolyl- and pyridyl-based organic molecules, azamacrocyclic and aminocarboxylic derivatives, and their conjugates to polypeptides or oligonucleotides. The purpose of this perspective is to highlight: (1) the differences in structure and composition between natural and synthetic multinuclear metallonucleases; (2) the design strategies of synthetic multinuclear metallonucleases; (3) the relationship between the structures and nucleolytic activities of synthetic multinuclear metallonucleases; and (4) the cooperativities between metal sites, and between metal sites and ligands in the courses of phospodiester linkage hydrolysis. A comparison illustrates unifying themes in the catalysis of phosphodiester linkage hydrolysis by natural and synthetic multinuclear metallonucleases. Indeed, there are features that converge about the chemistry that provides insight into how changes in metal ions and ligands of both natural and synthetic metallonucleases may lead to the same overall outcome of phosphodiester backbone cleavage. In addition, we will also discuss the solvation effect of synthetic multinuclear metallonucleases and the challenges that should be faced toward the development of synthetic multinuclear metallonucleases with DNA sequence or structure selectivity by applying the principles of coordination and enzymatic chemistry.
    [Abstract] [Full Text] [Related] [New Search]