Reaction of N-methyl-N′-nitro-N-nitrosoguanidine with protein: formation of nitroguanido derivatives

Abstract

When serum albumin is exposed to N-methyl-N′-nitro-N-nitrosoguanidine (NG) one of the main reactions is conversion of ε-amino groups of lysine to nitroguanido groups. This conversion results in a large increase in the extinction coefficient of the protein as well as an increase in electrophoretic mobility (toward the positive pole). The lysine content of the protein is reduced. Enzymatic hydrolysis of NG-treated protein liberates an ultraviolet-absorbing, ninhydrin positive compound with chromographic properties which are identical with those of nitrohomoarginine. The concentration of NG required to form at least one nitroguanido group in a significant fraction of protein molecules is very much greater than that required to inactivate transforming DNA in vitro or to kill various microorganisms.Further evidence for the formation of nitroguanido derivatives is provided by the observation that glycine reacts with NG to form nitroguanidoacetic acid.