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Article

A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes

1
Department of Medicinal Chemistry and Molecular Pharmacology, Institute for Drug Discovery, Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA
2
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Baghdad, Bab-almoadham, Baghdad 10047, Iraq
*
Author to whom correspondence should be addressed.
Academic Editor: Umesh R. Desai
Biomolecules 2021, 11(6), 854; https://doi.org/10.3390/biom11060854
Received: 12 April 2021 / Revised: 3 June 2021 / Accepted: 3 June 2021 / Published: 8 June 2021
(This article belongs to the Collection Feature Papers in Enzymology)
Protein arginine methyltransferases (PRMTs) play important roles in transcription, splicing, DNA damage repair, RNA biology, and cellular metabolism. Thus, PRMTs have been attractive targets for various diseases. In this study, we reported the design and synthesis of a potent pan-inhibitor for PRMTs that tethers a thioadenosine and various substituted guanidino groups through a propyl linker. Compound II757 exhibits a half-maximal inhibition concentration (IC50) value of 5 to 555 nM for eight tested PRMTs, with the highest inhibition for PRMT4 (IC50 = 5 nM). The kinetic study demonstrated that II757 competitively binds at the SAM binding site of PRMT1. Notably, II757 is selective for PRMTs over a panel of other methyltransferases, which can serve as a general probe for PRMTs and a lead for further optimization to increase the selectivity for individual PRMT. View Full-Text
Keywords: protein arginine methyltransferases; inhibitor; methyltransferase; competitive inhibitor protein arginine methyltransferases; inhibitor; methyltransferase; competitive inhibitor
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MDPI and ACS Style

Iyamu, I.D.; Al-Hamashi, A.A.; Huang, R. A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes. Biomolecules 2021, 11, 854. https://doi.org/10.3390/biom11060854

AMA Style

Iyamu ID, Al-Hamashi AA, Huang R. A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes. Biomolecules. 2021; 11(6):854. https://doi.org/10.3390/biom11060854

Chicago/Turabian Style

Iyamu, Iredia D.; Al-Hamashi, Ayad A.; Huang, Rong. 2021. "A Pan-Inhibitor for Protein Arginine Methyltransferase Family Enzymes" Biomolecules 11, no. 6: 854. https://doi.org/10.3390/biom11060854

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