Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, SC 29208, USA.
Chembiochem. 2010 Jun 14;11(9):1219-23. doi: 10.1002/cbic.201000209.
Protein arginine methyltransferases (PRMTs) catalyze the post-translational methylation of arginine residues. PRMT1 is the predominant mammalian isozyme, and is responsible for generating the majority of the asymmetrically dimethylated arginine found . The dysregulation of this enzyme has been implicated in heart disease and cancer; thus, its inhibition would be useful in the treatment of these diseases. Herein, we describe the most potent PRMT1 inhibitor described to date. This compound, denoted C21, is a chloroacetamidine-containing peptide that is able to irreversibly bind and inactivate the enzyme selectively. We have also shown that the coactivator activity of PRMT1 is selectively inhibited by the compound .
蛋白质精氨酸甲基转移酶（PRMTs）催化精氨酸残基的翻译后甲基化。PRMT1 是主要的哺乳动物同工酶，负责生成发现的大多数不对称二甲基化精氨酸。该酶的失调与心脏病和癌症有关；因此，其抑制作用将对这些疾病的治疗有用。在此，我们描述了迄今为止描述的最有效的 PRMT1 抑制剂。该化合物表示为 C21，是一种含有氯乙酰胺的肽，能够选择性地不可逆结合并失活该酶。我们还表明，该化合物选择性地抑制 PRMT1 的共激活剂活性。
