Eriksson, Staffan
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Abstract
Five novel 3-carboranyl thymidine analogues (3CTAs) were designed and synthesized for boron neutron capture therapy (BNCT) of cancer. Phosphorylation of all five 3CTAs was catalyzed by recombinant human thymidine kinase (hTK1) using adenosine triphosphate (ATP) as the phosphate donor. The obtained phosphorylation rates ranged from 4% to 64.5% relative to that of thymidine. The compound with the most favorable hTK1 binding properties had a k(cat)/K-M value of 57.4% relative to that of thymidine and an IC50 of inhibition of thymidine phosphorylation by hTK1 of 92 mu M. Among the five synthesized 3CTAs, this agent had also the overall most favorable physicochemical properties. Therefore, it may have the potential to replace N5-2OH, the current lead 3CTA, in preclinical studies. An in silico model for the binding of this compound to hTK1 was developed. (c) 2006 Elsevier Ltd. All rights reserved.
Keywords
3-carboranyl thymidine analogues (3CTAs); boron neutron capture therapy (BNCT); thymidine kinase 1 (TK1)
Published in
Bioorganic and Medicinal Chemistry
2006, volume: 14, number: 20, pages: 6886-6899
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
SLU Authors
UKÄ Subject classification
Veterinary Science
Animal and Dairy Science
Publication identifier
- DOI: https://doi.org/10.1016/j.bmc.2006.06.039
Permanent link to this page (URI)
https://res.slu.se/id/publ/11232