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Báo cáo khoa học: Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production

The protein arginine methyltransferase (PRMT) family of enzymes cata-lyzes the transfer of methyl groups from S-adenosylmethionine to the gua-nidino 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. | Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production Kevin Bonham1 Saskia Hemmers1 Yeon-Hee Lim2 Dawn M. Hill1 M. G. Finn2 and Kerri A. Mowen1 1 Department of Chemical physiology and Department of Immunology and MicrobialSciences The Scripps Research Institute La Jolla CA USA 2 Department of Chemistry and the Skaggs Institute for ChemicalBiology The Scripps Research Institute La Jolla CA USA Keywords cytokines inhibitors nuclear factor of activated T cells interacting protein 45 kDa NIP45 protein arginine methyltransferase T-helper cell Correspondence Kerri A. Mowen Department of Chemical Physiology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla CA 92037 USA Fax 1 858 784 9190 Tel 1 858 784 2248 E-mail kmowen@scripps.edu M. G. Finn Department of Chemistry and the Skaggs Institute for ChemicalBiology La Jolla CA 92037 USA Fax 1 858 784 8850 Tel 1 858 784 2087 E-mail mgfinn@scripps.edu Received 13 August 2009 revised 29 January 2010 accepted 22 February 2010 doi 10.1111 j.1742-4658.2010.07623.x The protein arginine methyltransferase PRMT family of enzymes catalyzes the transfer of methyl groups from S-adenosylmethionine to the gua-nidino 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. Structured digital abstract MINT-7710141 Prmtl uniprotkb Q63009 physically interacts MI 0915 with nỉp45 uni-protkb O09130 by anti tag coimmunoprecipitation MI 0007 MINT-7710127 Prmtl uniprotkb Q63009 physically interacts MI 0915 with Prmtl uni-protkb Q63009 by anti tag coimmunoprecipitation MI 0007 Introduction Although .