Exploration of the effect of sterically demanding 3'-amido substitution of 3'-deoxyadenosines towards inhibition of cyclin-dependent kinase 1.
With focus on exploring the structural demands of adenosine triphosphate pockets of different target enzymes, the 3'-amido-3'-deoxyadenosines 1-7 were synthesized. The inhibitory activity of these compounds on a selected cyclin-dependent kinase as model target in anticancer research was evaluated in vitro. A starfish oocyte enzyme based assay revealed a decreased inhibitory activity in comparison to adenosine. Consequently, the introduction of spacefilling lipophilic 3'-amido substituents alters the enzyme inhibition in an unfavorable manner.
Van Calenbergh
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Faculteit Farmaceutische Wetenschappen, Universiteit Gent, Belgium.
Link
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Kunick
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Herdewijn
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P
D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D009865:Oocytes / Q000201:enzymology; D013215:Starfish
D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D016203:CDC2 Protein Kinase