Title: Thymidine phosphorylase is noncompetitively inhibited by 5'-O-trityl-inosine (KIN59) and related compounds
Authors: Liekens, Sandra ×
Balzarini, Jan
Hernández, A I
De Clercq, Erik
Priego, E M
Camarasa, M J
Pérez-Pérez, M J #
Issue Date: Jan-2006
Publisher: Marcel Dekker
Series Title: Nucleosides, Nucleotides & Nucleic Acids vol:25 issue:9-11 pages:975-80
Conference: 10th European/12th International Meeting on Purines and Pyrimidines location:Prague, Czech Republic date:9-12 June 2005
Abstract: We found that 5'-O-trityl-inosine (KIN59) inhibits recombinant bacterial (E. coli) and human thymidine phosphorylase (TPase) with an IC50 of 44 microM and 67 microM, respectively. In contrast to previously described TPase inhibitors, KIN59 does not compete with thymidine (dThd) at the pyrimidine nucleoside-binding site or with inorganic phosphate (Pi) at the phosphate-binding site of the enzyme. These findings are strongly suggestive for the presence of an allosteric binding site at the enzyme. TPase is identical to the angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF). As such, PD-ECGF stimulates angiogenesis in the chick chorioallantoic membrane (CAM) assay. This angiogenic response was completely inhibited by KIN59. Inosine did not inhibit the enzyme or the angiogenic effect of TPase, confirming that the 5'-O-trityl group in KIN59 is essential for the observed effect. Our observations indicate that allosteric sites in TPase may regulate its biological activity.
ISSN: 1525-7770
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science