Synthesis of 2,6-Dimethoxyhydroquinone-3-mercaptoacetyl-peptide-chlorambucil Conjugates

This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized another two new DMQ-MA-peptide- chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-OMe, DMQ-MA-Lys(DMQ-MA)-Lys(CRB)-Arg-OMe. These peptide-chlorambucil conjugates were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF. The CRB in side chain was coupled by deblocking the lysyl-carbobenzyloxy protecting group Z and then reacting with the pentafluorophenyl ester of chlorambucil (CRB). Further study on cytotoxicity, DNA binding, and sequence specificity of DNA alkylation of these two new conjugates are investigating.