title: Preparation and analysis of oligonucleotides containing the c4'-oxidized abasic site and related mechanistic probes.
abstract: The C4'-oxidized abasic site (C4-AP) is produced by a variety of DNA damaging agents. This alkali labile lesion can exist in up to four diastereomeric cyclic forms, in addition to the acyclic keto-aldehyde. Synthetic oligonucleotides containing the lesion were prepared from a stable photochemical precursor. Chemical integrity of the lesion containing oligonucleotides was probed using phosphodiesterase lability. Analysis of the 3',5'-phosphate diester of the monomeric lesion released from single diastereomers of photolabile precursors by 1H NMR indicates that isomerization of the hemiacetal and/or hemiketal is rapid. The syntheses and characterization of oligonucleotides containing configurationally stable analogues of C4-AP, which serve as mechanistic probes for deciphering the structural basis of the biochemical and biological effects of the C4'-oxidized abasic lesion, are also described.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
authors.forename: Jaeseung
authors.initials: J
authors.lastname: Kim
authors.forename: Cortney R
authors.initials: CR
authors.lastname: Kreller
authors.forename: Marc M
authors.initials: MM
authors.lastname: Greenberg
mesh_terms: D001483:Base Sequence; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D010777:Photochemistry
chemical_list: D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides