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.
Morphologies of ceramic hollow fiber membranes prepared by a combined phase-inversion and sintering method were studied. The organic binder spinning solution containing suspended Al₂O₃ powders was spun to a hollow fiber precursor, which was then sintered at elevated temperatures( 300 ˚C, 1400 ˚C, 25 ˚C) in order to obtain the Al₂O₃ hollow fiber membranes. The spinning solution consisted of polyether sulfone (PES), N-methyl-2-pyrrolidone (NMP), which were used as polymer binder, solvent, respectively. The prepared Al₂O₃ hollow fiber membranes were characterized by a scanning electron microscope (SEM). It is believed that finger-like void formation in asymmetric ceramic membranes is initiated by hydrodynamically unstable vis
... Show MoreA study of the hadiths of supplication orchestration
This study deals with strategic maneuvering in advertisement from a pragmatic point of view found in some commercial advertisements in order to investigate and analyze the pragmatic devices that are used in the strategic maneuvering and stages. The study attempts to shed light on the most fuzzy areas in advertisements that is probably how the language of advertisements employed by advertisers to affect consumers positively. The primary goal of strategic maneuvering is to discover how the pragmatic devices have persuasive techniques that are used to gain a competitive advantage and more sales. This study is a contribution to the field of research in the language used in advertising. In this research, the effectiveness of strategic man
... Show MoreJudicial jurisprudence is one of the important legal solutions to address the shortcomings of legislation. Throughout its long history, human societies have known many cases in which the judge finds himself facing a legislative vacuum in addition to civil legal texts that are difficult for the judge to implement due to ambiguity or contradiction, which requires diligence. To rule on resolving disputes before him in order not to deny justice, but the judge in his jurisprudence was not absolute, but rather bound by certain controls represented by observing the wisdom of legislation on the one hand and taking into account the nature of the texts on the other side, and from here this research came to shed light on the jurisprudence and its cont
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