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.
ملخص البحث
تبحث الدراسھ عن تنفیذ افضل لمفھوم التعلم مدى الحیاة كھیكل موجھ للسیاسة التربویة في العراق بشكل عام وفي
التعلیم العالي بشكل خاص. تحدد الدراسة استراتجیات التعلم مدى الحیاة وتناقش اھمیتھ وسماتھ الرئیسیة لتسھیل
الوصول الى فرص تعلم متمیز و ملائم لحاجات الطلبة مدى الحیاة، كما تناقش دور الجامعة في تحقیق ھذا الھدف.
يعد الاقتصاد الياباني احد اكبر الاقتصادات الرأسمالية المتقدمة ويحتل المرتبة الثالثة بعد الاقتصاد الأمريكي واقتصاد الاتحاد الاوربي من حيث حجم الناتج المحلي الإجمالي والذي يكاد يقترب من (5) تريليون دولار سنويا.
لقد ادت التطورات المتلاحقة التي شهدها الاقتصاد العالمي وخاصة في حقل التمويل الدولي خلال العشرين سنة الاخيرة الى تصاعد وارتفاع في حجم وحركه رؤوس الاموال الدولية على اوسع نطاق بحيث ا
... Show MoreIl semble que Khattabi était un linguiste, avec un endroit linguistique pour comprendre les textes de conversations et des mots étranges en particulier. Langue, et chacun avait ses arguments et ses preuves. Ses corrections incluaient la mélodie dans les mouvements, telle qu'une dilution plus serrée, la dilution de l'agitateur, le remplacement d'un autre mouvement, ou une autre rotation des mouvements, et le changement de structure morphologique du mot qui en résultait, ainsi que l'alerte sur les conséquences des lettres, Certaines de ces erreurs sont dues à la langue, et certaines sont considérées comme un type de déformation ou de fausse représentation connue de certains spécialistes, ce qui constitue un précédent louable
... Show MoreIron is one of the abundant elements on earth that is an essential element for humans and may be a troublesome element in water supplies. In this research an AAN model was developed to predict iron concentrations in the location of Al- Wahda water treatment plant in Baghdad city by water quality assessment of iron concentrations at seven WTPs up stream Tigris River. SPSS software was used to build the ANN model. The input data were iron concentrations in the raw water for the period 2004-2011. The results indicated the best model predicted Iron concentrations at Al-Wahda WTP with a coefficient of determination 0.9142. The model used one hidden layer with two nodes and the testing error was 0.834. The ANN model coul
... Show MoreNew series of 4,4'-((2-(Aryl)-1H-benzo[d]imidazole-1,3(2H)-diyl)bis(methylene))Diphenol(3a-g) was successfully synthesized from cyclization of the reduction product of bis Schiff bases (2) with aryl aldehydes bearing phenolic hydroxyl in the presence of acetic acid. The structure of these compounds was identified from FT-IR, 1H NMR, 13C NMR and EIMs. The Antioxidant capability was screened by DPPH and FRAP assays. Both assays showed antioxidant capability more than BHT as well. Compounds 3b and 3c showed antioxidant capacity slightly less than ascorbic acid. The docking study for theses compound was carried out as III DNA polymerase inhibitor. The results of docking demonstrated that the increase in hinderances around phenolic hydr
... Show MoreFusidic acid (FA) is a well-known pharmaceutical antibiotic used to treat dermal infections. This experiment aimed for developing a standardized HPLC protocol to determine the accurate concentration of fusidic acid in both non-ionic and cationic nano-emulsion based gels. For this purpose, a simple, precise, accurate approach was developed. A column with reversed-phase C18 (250 mm x 4.6 mm ID x 5 m) was utilized for the separation process. The main constituents of the HPLC mobile phase were composed of water: acetonitrile (1: 4); adjusted at pH 3.3. The flow rate was 1.0 mL/minute. The optimized wavelength was selected at 235 nm. This approach achieved strong linearity for alcoholic solutions of FA when loaded at a serial concentrati
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