Abstract
The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N(6)-amino moiety favors the inhibition of DNMT3b2 enzyme.
MeSH terms
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors*
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DNA (Cytosine-5-)-Methyltransferases / metabolism
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Humans
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S-Adenosylhomocysteine / chemical synthesis*
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S-Adenosylhomocysteine / chemistry
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S-Adenosylhomocysteine / pharmacology
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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S-Adenosylhomocysteine
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNA (cytosine-5-)-methyltransferase 3b2, human
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DNMT1 protein, human