Mechanism of action of the nitrosoureas--IV. Synthesis of the 2-haloethylnitrosourea-induced DNA cross-link 1-(3-cytosinyl),2-(1-guanyl)ethane

Biochem Pharmacol. 1990 Jan 1;39(1):33-6. doi: 10.1016/0006-2952(90)90645-2.

Abstract

The 2-haloethylnitrosoureas have been shown to form the cross-linked structure 1-(3-cytosinyl),2-(1-guanyl)ethane in DNA. This cross-link has now been synthesized by the reaction of O6-(2-fluoroethyl)guanosine with deoxycytidine in dimethyl sulfoxide followed by removal of the sugars by acid hydrolysis. This synthetic route supports the mechanism for cross-link formation in DNA that involves an initial attack on the O6-position of guanine, followed by a rearrangement and subsequent reaction with cytosine. It also provides a practical route to the synthesis of 1-(3-cytosinyl),2-(1-guanyl)ethane for studies involving formation of this cross-link in DNA.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents*
  • Chemical Phenomena
  • Chemistry
  • Cross-Linking Reagents*
  • DNA / drug effects*
  • Deoxycytidine
  • Dinucleoside Phosphates / chemical synthesis*
  • Guanosine / analogs & derivatives
  • Mass Spectrometry
  • Nitrosourea Compounds / pharmacology*
  • Spectrophotometry, Ultraviolet

Substances

  • Antineoplastic Agents
  • Cross-Linking Reagents
  • Dinucleoside Phosphates
  • Nitrosourea Compounds
  • Deoxycytidine
  • Guanosine
  • 1-(3-cytosinyl)-2-(1-guanyl)ethane
  • fluoroethylguanosine
  • DNA