IN-VITRO REACTIVITY OF THE ANTINEOPLASTIC CARMUSTIN AND ACROLEIN WITHMODEL PEPTIDES

The in vitro interaction of the antineoplastic drug 1,3-bis-(2-chloroe thyl)-1-nitrosourea (BCNU) and acrolein with model peptides has been i nvestigated in order to provide a detailed description of their electr ophilic reactivity towards biological macromolecules. Following incuba tion with these substances, the modified species were separated by HPL C and identified by fast atom bombardment mass spectrometry, whereas t he reactive amine acids within the peptide structure were assigned by tandem mass spectrometry. incubation with BCNU led essentially to the formation of an N-terminal carbamoyl derivative that slowly decomposed to form three isomeric structures and a very minor ethylated adduct. Alkylation with acrolein gave rise to a mixture of different adducts d ue to the reaction of both the double bond and the carbonyl group, Two species containing intramolecular cross-links were also observed. The se results constitute the prerequisite for in vitro and in vivo studie s on the modification of haemoglobin in patients following treatment w ith antineoplastic drugs. (C) Munksgaard 1997.