EXOCYCLIC ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES

  • Breslauer, Kenneth (PI)
  • Breslauer, Kenneth (PI)
  • De Los Santos, Carlos Raul (PI)
  • Kisker, Caroline (PI)
  • Iden, Charles (PI)
  • Grollman, Arthur (PI)
  • Grollman, Arthur (PI)
  • Johnson, Francis (PI)
  • Grollman, Arthur (PI)
  • Eisenberg, Moises (PI)
  • Iden, Charles (PI)
  • Johnson, Francis (PI)
  • Eisenberg, Moises (PI)
  • Grollman, Arthur (PI)
  • GROLLMAN, ARTHUR PATRICK (PI)

Project Details

Description

The analytical chemistry and organic syntheses developed in this Project
provide an essential underpinning for this Program. Experiments are
designed to identify chemically-modified nucleotides formed by the reac-
tions of certain chemotherapeutic agents and genotoxic compounds with
native DNA. The mechanism and sequence specificity of cross-link formation
will be investigated using sequence-defined duplex oligodeoxynucleotides.
Exocyclic adducts, alkylation products, and cross-linked deoxynucleotides
will be identified using advanced detection techniques of FAB mass spectro-
metry, thermospray LC/MS, nuclear magnetic resonance, and high performance
and liquid chromatography.

In additional experiments, organic syntheses leading to single strand
oligodeoxynucleotides of defined base sequence containing a single chemi-
cally-modified site are proposed. Known exocyclic products of the reaction
of DNA with BCNU, acrolein, and vinyl chloride, will be synthesized,
converted to their phosphoramidites and incorporated into synthetic
oligodeoxynucleotides using solid state techniques. New protecting groups
for protection of the nucleoside phosphoramidites used in solid state DNA
synthesis will be developed. This will permit the inclusion of the alkali-
sensitive adducts into synthetic oligomers.
StatusFinished
Effective start/end date1/1/017/31/10

ASJC

  • Medicine(all)
  • Analytical Chemistry
  • Genetics
  • Chemical Engineering(all)
  • Chemistry(all)
  • Molecular Biology
  • Biophysics
  • Structural Biology
  • Spectroscopy
  • Cancer Research
  • Physical and Theoretical Chemistry