共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
3.
Esther K. Schmitt Meliana Riwanto Vasan Sambandamurthy Silvio Roggo Charlotte Miault Christian Zwingelstein Philipp Krastel Christian Noble David Beer Srinivasa P. S. Rao Melvin Au Pornwaratt Niyomrattanakit Viviam Lim Jun Zheng Douglas Jeffery Kevin Pethe Luis R. Camacho 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2011,123(26):6011-6013
4.
5.
6.
7.
8.
9.
10.
11.
12.
H. Ümit Kaniskan Magdalena M. Szewczyk Zhengtian Yu Mohammad S. Eram Xiaobao Yang Keith Schmidt Xiao Luo Miao Dai Feng He Irene Zang Ying Lin Steven Kennedy Fengling Li Elena Dobrovetsky Aiping Dong David Smil Sun‐Joon Min Melissa Landon Jennifer Lin‐Jones Xi‐Ping Huang Bryan L. Roth Matthieu Schapira Peter Atadja Dalia Barsyte‐Lovejoy Cheryl H. Arrowsmith Peter J. Brown Kehao Zhao Jian Jin Masoud Vedadi 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2015,127(17):5255-5259
PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is essential for maturation of ribosomes, may have a role in lipogenesis, and is implicated in several diseases. A potent, selective, and cell‐active PRMT3 inhibitor would be a valuable tool for further investigating PRMT3 biology. Here we report the discovery of the first PRMT3 chemical probe, SGC707, by structure‐based optimization of the allosteric PRMT3 inhibitors we reported previously, and thorough characterization of this probe in biochemical, biophysical, and cellular assays. SGC707 is a potent PRMT3 inhibitor (IC50=31±2 nM , KD=53±2 nM ) with outstanding selectivity (selective against 31 other methyltransferases and more than 250 non‐epigenetic targets). The mechanism of action studies and crystal structure of the PRMT3‐SGC707 complex confirm the allosteric inhibition mode. Importantly, SGC707 engages PRMT3 and potently inhibits its methyltransferase activity in cells. It is also bioavailable and suitable for animal studies. This well‐characterized chemical probe is an excellent tool to further study the role of PRMT3 in health and disease. 相似文献
13.
Changsheng Wu Helga U. vanderHeul Alexey V. Melnik Jens Lübben Pieter C. Dorrestein Adriaan J. Minnaard Young Hae Choi Gilles P. vanWezel 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(9):2835-2840
The angucyclines form the largest family of polycyclic aromatic polyketides, and have been studied extensively. Herein, we report the discovery of lugdunomycin, an angucycline‐derived polyketide, produced by Streptomyces species QL37. Lugdunomycin has unique structural characteristics, including a heptacyclic ring system, a spiroatom, two all‐carbon stereocenters, and a benzaza‐[4,3,3]propellane motif. Considering the structural novelty, we propose that lugdunomycin represents a novel subclass of aromatic polyketides. Metabolomics, combined with MS‐based molecular networking analysis of Streptomyces sp. QL37, elucidated 24 other rearranged and non‐rearranged angucyclines, 11 of which were previously undescribed. A biosynthetic route for the lugdunomycin and limamycins is also proposed. This work demonstrates that revisiting well‐known compound families and their producer strains still is a promising approach for drug discovery. 相似文献
14.
15.
16.
17.
18.