title: Development of triazene prodrugs for ADEPT strategy: new insights into drug delivery system based on carboxypeptidase G2 activation.
abstract: Six novel urea triazene prodrugs have been synthesized to apply in antibody-directed enzyme prodrug therapy (ADEPT). The chemical and plasmatic stability of l-glutamate triazene prodrugs were evaluated and the chemical reactivity was mainly attributed to an intramolecular catalysis promoted by the neighbouring carboxylate group of the glutamic moiety. These prodrugs showed an elevated binding to plasma proteins. The L-glutamate triazenes were evaluated as prodrugs of the alkylating agent's monomethyltriazenes, by activation of the bacterial enzyme carboxypeptidase G2 (CPG2). The synthesized prodrugs have been shown to be good substrates for CPG2, and therefore new candidates for ADEPT strategy.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Verónica
authors.initials: V
authors.lastname: Capucha
authors.forename: Eduarda
authors.initials: E
authors.lastname: Mendes
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Francisco
authors.forename: M Jesus
authors.initials: MJ
authors.lastname: Perry
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D001419:Bacteria / Q000201:enzymology; D004337:Drug Carriers / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014226:Triazenes / Q000737:chemistry*; D011623:gamma-Glutamyl Hydrolase / Q000378:metabolism*
chemical_list: D000477:Alkylating Agents; D000906:Antibodies; D004337:Drug Carriers; D011355:Prodrugs; D012709:Serum Albumin; D014226:Triazenes; D018698:Glutamic Acid; D011623:gamma-Glutamyl Hydrolase