Potential latentiation forms of biologically active compounds based on action of leucine aminopeptidase. Dipeptide derivatives of the tricycloaliphatic alpha-amino acid, adamantanine.
Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leucyladamantanine appeared to be absorbed in vivo as evidenced by its appearance in the uring following intraperitoneal administration, they were not hydrolyzed by a purified preparation of leucine aminopeptidase in vitro. Indeed, they were inhibitors of this enzyme. Adamantanylglycine, adamantanyl-L-leucine, and adamantanyl-L-phenylalanine were also not hydrolyzed by leucine aminopeptidase.
D000547:Amantadine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D001682:Biological Availability; D004151:Dipeptides / Q000138:chemical synthesis* / Q000627:therapeutic use; D006868:Hydrolysis; D007700:Kinetics; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors*; D007939:Leukemia L1210 / Q000188:drug therapy; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains
D004151:Dipeptides; D000547:Amantadine; D007931:Leucyl Aminopeptidase