| Abstract
| - The design and synthesis of potent thiocarbamate inhibitors for carboxypeptidase G2 aredescribed. The best thiocarbamate inhibitor N-(p-methoxybenzenethiocarbonyl)amino-l-glutamic acid 6d, chosen for preliminary investigations of in vitro antibody-directed enzymeprodrug therapy (ADEPT), abrogated the cytotoxicity of a combination of A5B7−carboxypeptidase G2 conjugate and prodrug PGP (N-p-{N,N-bis (2-chloroethyl)amino}phenoxycarbonyl-l-glutamate) toward LS174T cells. This is the first report of a small-molecule enzyme inhibitorproposed for use in conjunction with the ADEPT approach.
|
