Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).

  • Authors:
    • E Kun
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  • Published online on: August 1, 1998     https://doi.org/10.3892/ijmm.2.2.131
  • Pages: 131-273
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Abstract

The cellular coenzymatic role of NAD, being a pleiotropic cofactor for diverse cellular reactions, is extended to poly(ADP-ribose) and to the highly abundant nuclear protein, poly(ADP-ribose) polymerase, with special focus on the pharmacological action of ligands on the latter. The polymer is defined to possess a helical configuration. From direct analyses of the polymer under physiological conditions, it is concluded that the polymerase is dormant in normal tissues, but is activated under certain pathological conditions: malignancy, retroviral integrate containing cells, and in a variety of inflammatory states. The interaction of poly(ADP-ribose) polymerase ligands with the DNA component of the active poly (ADP-ribose) polymerase - DNA complex is shown. A major cellular function of the poly(ADP-ribose) polymerase protein is its binding capacity to a large number of nuclear proteins and DNA sites, an effect which is induced by drugs that inhibit the polymerase activity. The malignancy-reverting effect of poly(ADP-ribose) polymerase ligand drugs is illustrated in chemically and oncovirally transformed cancer cells. The poly(ADP-ribose) polymerase ligand-induced cessation of HIV replication is analyzed. Peroxynitrite-induced DNA damage-initiated pathological responses are shown to be inhibited by a specific poly(ADP-ribose) polymerase ligand. The irreversibly acting C-NO drugs oxidize asymmetric zinc fingers [poly(ADP-ribose) polymerase, HIV gag-precursor protein] and act as anti-cancer and anti-HIV agents, an effect that is regulated by cellular concentration of GSH.

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Aug 1998
Volume 2 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kun E: Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).. Int J Mol Med 2: 131-273, 1998
APA
Kun, E. (1998). Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).. International Journal of Molecular Medicine, 2, 131-273. https://doi.org/10.3892/ijmm.2.2.131
MLA
Kun, E."Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).". International Journal of Molecular Medicine 2.2 (1998): 131-273.
Chicago
Kun, E."Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).". International Journal of Molecular Medicine 2, no. 2 (1998): 131-273. https://doi.org/10.3892/ijmm.2.2.131