A Chemical Strategy to Trap and Identify Proteins That May Regulate Promoter Hypermethylation in Breast Cancer

Abstract

With the support from this grant we have been developing photocross-linking DNA base analogues to trap and identify DNMTs and interacting proteins on specific promoter DNA. To this end Diazirine photophore was introduced into either the major or minor groove of DNA as a photocross linking group via a convertible nucleoside methodology. The resulting DNA probes efficiently cross linked with the E. coli DNA adenine methyltransferase (EcoDam). The diazirine photophore possesses clear advantages over other photocross linking groups previously installed on DNA in that it has the least steric hindrance and efficiently generates a carbene intermediate that non-specifically cross links with protein residues nearby in high efficiency. We have also applied the method to human cell extracts and obtained very promising results. Based on this early success we are working on the BRCA1 promoter DNA and hope to identify the DNMT that works on this promoter in the near future.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2007
Accession Number
ADA475123

Entities

People

  • Chuan He

Organizations

  • University of Chicago

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Alcohols
  • Amines
  • Breast Cancer
  • Chemical Synthesis
  • Chemistry
  • Efficiency
  • Magnetic Resonance
  • Mass Spectrometry
  • Materials
  • Nuclear Magnetic Resonance
  • Nucleic Acids
  • Nucleosides
  • Organic Chemistry
  • Proteins
  • Tissue Extracts

Readers

  • Molecular Genetics
  • Molecular and genetic basis of cancer.
  • Organic Chemistry