Synthesis and characterization of O6-(2-chloroethyl)guanine: a putative intermediate in the cytotoxic reaction of chloroethylnitrosoureas with DNA.
The chloroethylnitrosoureas are useful antitumor agents which evidently exert a significant part of their cytotoxic action through the formation of a unique 1-(3-deoxycytidyl), 2-(1-deoxyguanosinyl)ethane cross-link in DNA. It has been suggested that this cross-link is formed from O6-(2-chloro-ethyl)guanine, an initial product of DNA alkylation by the chloroethylnitrosoureas; however, O6-(2-chloroethyl)guanine has never been described. We have synthesized this derivative from the reaction of thionyl chloride with O6-(2-hydroxyethyl)guanine, and have found that it decomposes to 1-(2-hydroxyethyl)guanine through an intermediate, presumably 1,O6-ethanoguanine. Its half life at 37 degrees and pH 7.4 is 17.8 min.
Parker
S
S
Department of Medicine, Albany Medical College, Albany, New York 12208.
Kirk
M C
MC
Ludlum
D B
DB
D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004247:DNA; D004249:DNA Damage; D005038:Ethylnitrosourea / Q000031:analogs & derivatives*; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006863:Hydrogen-Ion Concentration; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
C047691:O(6)-(2-chloroethyl)guanine; C017139:1-(2-chloroethyl)-1-nitrosourea; D006147:Guanine; D004247:DNA; D005038:Ethylnitrosourea