A versatile approach towards regioselective platinated DNA sequences

Chemistry. 2003 Apr 14;9(8):1823-7. doi: 10.1002/chem.200390209.

Abstract

Undesired N(7) platination of 2'-deoxyguanosine residues at predetermined sites in an oligodeoxynucleotide (ODN) sequence is prevented by applying the sterically demanding diphenylcarbamoyl (DPC) as an O(6)-protecting group. The presence of a base-labile oxalyl linker between the immobilized 3'-nucleotide and controlled pore glass (CPG) allows cleavage of the protected ODN from the support and leaves DPC protection unaffected. This method provides an ODN with specifically blocked guanine-N(7) sites for platination. In the hexanucleotides prepared in this study, 5'-GGBGGT-3'(for B=T, C and A), a platinum GG adduct is introduced at G4,G5. These site-specific platinated hexamers were isolated in a yield of 65 %, and were fully characterized by using reversed-phase HPLC (high performance liquid chromotography), LCMS (liquid chromatography-mass spectrometry), MALDI-TOF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry), PAGE (polyacrylamide gel electrophoresis) and Maxam-Gilbert sequencing analysis.

MeSH terms

  • Base Sequence
  • Carbamates / chemistry
  • Chromatography, High Pressure Liquid / methods
  • Cross-Linking Reagents / chemistry
  • DNA / chemistry*
  • DNA Adducts / chemistry
  • Electrophoresis, Polyacrylamide Gel
  • Glass
  • Oligodeoxyribonucleotides / chemistry
  • Organoplatinum Compounds / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Stereoisomerism

Substances

  • Carbamates
  • Cross-Linking Reagents
  • DNA Adducts
  • Oligodeoxyribonucleotides
  • Organoplatinum Compounds
  • DNA
  • carbamic acid