Abstract
The protein arginine methyltransferase (PRMT) family of enzymes catalyzes the transfer of methyl groups from S-adenosylmethionine to the guanidino nitrogen atom of peptidylarginine to form monomethylarginine or dimethylarginine. We created several less polar analogs of the specific PRMT inhibitor arginine methylation inhibitor-1, and one such compound was found to have improved PRMT inhibitory activity over the parent molecule. The newly identified PRMT inhibitor modulated T-helper-cell function and thus may serve as a lead for further inhibitors useful for the treatment of immune-mediated disease.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation / drug effects
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Cells, Cultured
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology*
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Histones
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Humans
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Interferon-gamma / biosynthesis*
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Interferon-gamma / immunology
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Interleukin-4 / biosynthesis*
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Methylation
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Mice
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Mice, Inbred BALB C
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Molecular Structure
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Promoter Regions, Genetic
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Protein-Arginine N-Methyltransferases / antagonists & inhibitors*
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Structure-Activity Relationship
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / drug effects*
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T-Lymphocytes, Helper-Inducer / immunology*
Substances
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Enzyme Inhibitors
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Histones
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Interleukin-4
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Interferon-gamma
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Protein-Arginine N-Methyltransferases