title: Dipeptidyl-peptidase IV (DPP IV/CD26)-activated prodrugs: a successful strategy for improving water solubility and oral bioavailability.
abstract: In the search of novel enzyme-based prodrug approaches to improve pharmacological properties of therapeutic drugs such as solubility and bioavailability, dipeptidyl-peptidase IV (DPP IV, also termed as CD26) enzyme activity provides a previously unexplored successful prodrug strategy. This review covers key aspects of the enzyme useful for the design of CD26-directed prodrugs. The proof-of-concept of this prodrug technology is provided for amine-containing agents by directly linking appropriate di- (or oligo)peptide moieties to a free amino group of a non-peptidic drug through an amide bond which is specifically hydrolized by DPP IV/CD26. Special emphasis is also made in discussing the design and synthesis of more elaborated tripartite prodrug systems, for further extension of the strategy to hydroxy-containing drugs. The application of this technology to improve water solubility and oral bioavailability of prominent examples of antiviral nucleosides is highlighted.
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Velázquez
authors.forename: Sonia
authors.initials: S
authors.lastname: de Castro
authors.forename: Alberto
authors.initials: A
authors.lastname: Diez-Torrubia
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Institute of Medicinal Chemistry (IQM-CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain. sonsoles@iqm.csic.es.
authors.forename: María-José
authors.initials: MJ
authors.lastname: Camarasa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D011355:Prodrugs; D014867:Water; D018819:Dipeptidyl Peptidase 4