Alkylating esters X. The reaction of some aziridine alkylating agents with methionine and S-methyl cysteine

Two biologically active aziridine ring-containing compounds, N,N-ethylene urethane (I) and N,N-ethylene urea (II), have been shown to react with methionine in dilute phosphate buffer (pH 7.4) at 37°C. Degradative procedures indicate that the aziridine ring effectively alkylates the thio ether group of methionine and other thio ether-containing amino acids to produce sulphonium salts (V). By using ³⁵S]methionine, the sulphonium salts have been shown to be quite stable under physiological conditions ($\text{t}{}_{\mathrm{<mtext>built1</mtext><mtext>2</mtext>}}$ 7–9 days) hydrolysing to convert the methionine residue to homoserine.It is proposed that similar alkylations of methionyl residues in vivo by aziridine-alkylating agents may explain the complex, and as yet unknown, metabolic fate of the aziridine ring and could also be a factor contributing to the diverse effects that these agents have on living cells.