Title: Some 6-aza-5-substituted-2 '-deoxyuridines show potent and selective inhibition of herpes simplex virus type 1 thymidine kinase
Authors: Basnak, I ×
Sun, M
Hamor, TA
Focher, F
Verri, A
Spadari, S
Wroblowski, B
Herdewijn, Piet
Walker, RT #
Issue Date: 1998
Publisher: Marcel dekker inc
Series Title: Nucleosides nucleotides & nucleic acids vol:17 issue:1-3 pages:187-206
Abstract: The synthesis and X-ray crystal structures of a series of 5-substituted-6-aza-2'-deoxyuridines is reported. These nucleoside analogues inhibit the phosphorylation of thymidine by HSV-1 TK but have no effect on the corresponding human enzyme. Detailed examination of one analogue proves it to be a competitive inhibitor of thymidine with a Ki of 0.34 mu M and is a very poor substrate. The analogues are not substrates for the enzyme and also do not inhibit the degradation of thymidine by thymidine phosphorylase. Molecular modelling showed that the inhibitors fit well in the active site of HSV-1 TK, provided the conformation of the sugar moiety is the same for thymidine in the complex.
ISSN: 0732-8311
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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