Latentiated forms of the transport-inhibitory alpha-amino acid adamantanine

N-(gamma-L-Glutamyl)adamantanine (Ic) and N-hydroxyadamantanine (Ib) were synthesized as latentiated forms of the transport-inhibitory alpha-amino acid adamantanine (Ia), and their biological properties were evaluated. Inhibition of the growth of P-388 tumor cells by Ib was comparable with that of the antitumor agent N-hydroxycycloleucine (IIb). In contrast, Ic was inactive in this system, presumably because it was not a substrate for gamma-glutamyltranspeptidase. Nevertheless, the concept proposed here of using the enzyme, gamma-glutamyltranspeptidase, to latentiate drugs in vivo by synthetic gamma-glutamylation of an amino or hydroxyl group on the drug molecule appears to be worthy of further exploration.