Abstract
Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhibitory activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Arabinonucleosides / chemical synthesis*
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Arabinonucleosides / pharmacology
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Catalytic Domain
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Mitochondria / enzymology*
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Models, Molecular
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Structure-Activity Relationship
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Thymidine Kinase / antagonists & inhibitors*
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Viral Proteins / antagonists & inhibitors
Substances
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Arabinonucleosides
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Enzyme Inhibitors
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Viral Proteins
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thymidine kinase 2
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Thymidine Kinase