Publication
Title
Application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to different amine-containing drugs
Author
Abstract
Here we explore the applicability of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to a variety of amine-containing drugs. Efficient procedures have been developed for the synthesis of dipeptide and tetrapeptide amide prodrugs including N-acylation protocols of the exocyclic amino function of cytidine and adenosine nucleosides. Our studies demonstrated that XaaPro dipeptides linked to a free amino group present on an aromatic ring or on a sugar entity are prodrugs that efficiently release the parent drug upon conversion by purified DPPIV/CD26 as well as soluble DPPIV/CD26 in bovine and human serum. Vildagliptin, a specific inhibitor of DPPIV/CD26, was able to completely block the hydrolysis of the prodrugs in the presence of purified CD26 but also in human and bovine serum. When the amino group is present on a pyrimidine or purine ring, the dipeptide derivatives are chemically unstable, whereas the tetrapeptide derivatives (i.e., ValProValPro or ValAlaValPro) were much more stable in solution and efficiently converted to the parent drug by the action of DPPIV/CD26. This DPPIV/CD26-directed prodrug technology can be useful to increase solubility of the parent drug molecules and/or to allow better formulation properties.
Language
English
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Publication
Washington, D.C. : 2010
ISSN
0022-2623 [print]
1520-4804 [online]
DOI
10.1021/JM901590F
Volume/pages
53 :2 (2010) , p. 559-572
ISI
000273672100003
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 11.02.2010
Last edited 25.05.2022
To cite this reference