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

Abstract

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 degree C. Degradative procedures indicate that the aziridine ring effectively alylates 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 (t1/2 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 al yet unknwn, metabolic fate of the aziridine ring and could also be a factor contributing to the diverse effects that these agents have on living cells.