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.
Keywords: Amine-containing drugs, CD26 prodrugs, dipeptidyl peptidase IV, hydroxy-containing drugs, oral bioavailability, peptides, stability, water solubility.
Current Medicinal Chemistry
Title:Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability
Volume: 22 Issue: 8
Author(s): Sonsoles Velazquez, Sonia de Castro, Alberto Diez-Torrubia, Jan Balzarini and María-Jose Camarasa
Affiliation:
Keywords: Amine-containing drugs, CD26 prodrugs, dipeptidyl peptidase IV, hydroxy-containing drugs, oral bioavailability, peptides, stability, water solubility.
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.
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Cite this article as:
Velazquez Sonsoles, de Castro Sonia, Diez-Torrubia Alberto, Balzarini Jan and Camarasa María-Jose, Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability, Current Medicinal Chemistry 2015; 22 (8) . https://dx.doi.org/10.2174/0929867322666150114163449
DOI https://dx.doi.org/10.2174/0929867322666150114163449 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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