NITROGEN-MUSTARD MECHLORETHAMINE FIXES THE Z-CONFORMATION IN POLY[D(G-C)]POLY[D(G-C)] AND PLASMID DNA

The reaction of poly[d(G-C)].poly[d(G-C)] and a (dG-dC)10 insert in the plasmid pGC20 with N-methyl-bis(2-chloroethyl)amine (the nitrogen mustard mechlorethamine) was investigated. It was shown that mechlorethamine does not initiate a B-Z transition in the polynucleotide but fixes the Z-conformer of poly[d(G-C)]. poly[d(G-C)] under conditions in which it can exist. In the case of plasmid pGC20 DNA the reaction with mechlorethamine also leads to fixation of the Z-form of the (dG-dC) insert. The rate constant of the reaction of guanine in the nucleotide (k = 9.0.10(-3) min-1) is less than the rate constant of fixation of the Z-form the (dG-dC) insert in the plasmid (k1 = 2.8.10(-2) min-1), which is explained by the greater frequency of formation of the diguanyl derivative in opposite strands of DNA. It is suggested that embichen fixes the Z-conformer of DNA not only in vitro but also in vivo.