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DNA polymerases as therapeutic targets

Anthony J Berdis1

  • 1Department of Pharmacology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. ajb15@case.edu

Biochemistry
|July 23, 2008
PubMed

Insights

Targeting DNA replication by inhibiting DNA polymerases offers therapeutic potential for cancer and infections. This review summarizes agents that block polymerase activity, including nucleoside analogues, for treating diseases.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Uncontrolled DNA replication is implicated in various diseases, including cancer and infections.
  • DNA polymerases are key enzymes in DNA replication and thus represent critical therapeutic targets.
  • Inhibiting DNA polymerase activity offers a strategy for developing novel treatments.

Purpose of the Study:

  • To review therapeutic agents targeting DNA polymerase activity.
  • To discuss the mechanism of action, structure-activity relationships, and resistance of polymerase inhibitors.
  • To explore new therapeutic approaches targeting DNA repair and translesion synthesis polymerases.

Main Methods:

  • Literature review of therapeutic agents targeting DNA polymerases.
  • Discussion of biological function and mechanism of polymerases.
  • Analysis of nucleoside and non-nucleoside inhibitors for antiviral and anticancer applications.

Main Results:

  • Nucleoside analogues are effective inhibitors of viral and cancer-associated polymerases.
  • Understanding structure-activity relationships aids in rational drug design.
  • Resistance mechanisms and toxicity are critical considerations for therapeutic development.

Conclusions:

  • Inhibitors of DNA polymerases are valuable therapeutic agents for viral infections and cancer.
  • Targeting DNA repair and translesion synthesis polymerases presents a promising new avenue for anticancer therapy.
  • Further research into selective polymerase inhibition can lead to more effective and safer treatments.

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