Rational Inhibitors of DNA Base Excision (BER) Enzymes: New Tools for Elucidating the Role of BER in Cancer Chemotherapy

Abstract

In this funding period we have completed Task 1 of the approved Statement of Work which seeks to develop useful inhibitor scaffolds for the DNA repair enzyme uracil DNA glycosylase (UDG). In addition, we have performed groundbreaking studies that shed light on the molecular basis of substrate recognition by UDG. These new studies provide exciting avenues for rational inhibitor development with potential for anticancer therapy. Major findings in this period include the synthesis and screening of new bipartite transition state-based inhibitors for UDG, and the exploration of the roles of hydrogen bonding and molecular flexibility in specific recognition by the enzyme. This work has resulted in two publications during this period.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2004
Accession Number
ADA424155

Entities

People

  • Daniel J. Krosky
  • James T. Stivers

Organizations

  • Johns Hopkins University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biochemistry
  • Chemical Synthesis
  • Chemistry
  • Chemotherapy
  • Crystal Structure
  • Dissociation
  • Dna Repair Enzymes
  • Escherichia Coli
  • Free Energy
  • Inhibitors
  • Mass Spectrometry
  • Nucleosides
  • Nucleotides
  • Organic Chemistry
  • Recognition
  • Spectra
  • Spectroscopy

Readers

  • Molecular Genetics
  • Oncology
  • Technical Research and Report Writing.

Technology Areas

  • Biotechnology