Design, synthesis and cellular metabolism study of 4'-selenonucleosides
Jinha Yu1, Pramod K Sahu1, Gyudong Kim1
1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Background:
4'-seleno-homonucleosides were synthesized as next-generation nucleosides, and their cellular phosphorylation was studied to confirm the hypothesis that bulky selenium atom can sterically hinder the approach of cellular nucleoside kinase to the 5'-OH for phosphorylation.
Results:
4'-seleno-homonucleosides (n = 2), with one-carbon homologation, were synthesized through a tandem seleno-Michael addition-SN2 ring cyclization. LC-MS analysis demonstrated that they were phosphorylated by cellular nucleoside kinases, resulting in anticancer activity.
Conclusion:
The bulky selenium atom played a key role in deciding the phosphorylation by cellular nucleoside kinases. [Formula: see text].
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