152922-65-1Relevant articles and documents
Tracking the Dynamic Folding and Unfolding of RNA G-Quadruplexes in Live Cells
Chen, Xiu-Cai,Chen, Shuo-Bin,Dai, Jing,Yuan, Jia-Hao,Ou, Tian-Miao,Huang, Zhi-Shu,Tan, Jia-Heng
, p. 4702 - 4706 (2018)
Because of the absence of methods for tracking RNA G-quadruplex dynamics, especially the folding and unfolding of this attractive structure in live cells, understanding of the biological roles of RNA G-quadruplexes is so far limited. Herein, we report a new red-emitting fluorescent probe, QUMA-1, for the selective, continuous, and real-time visualization of RNA G-quadruplexes in live cells. The applications of QUMA-1 in several previously intractable applications, including live-cell imaging of the dynamic folding, unfolding, and movement of RNA G-quadruplexes and the visualization of the unwinding of RNA G-quadruplexes by RNA helicase have been demonstrated. Notably, our real-time results revealed the complexity of the dynamics of RNA G-quadruplexes in live cells. We anticipate that the further application of QUMA-1 in combination with appropriate biological and imaging methods to explore the dynamics of RNA G-quadruplexes will uncover more information about the biological roles of RNA G-quadruplexes.
Quinoline-galactose hybrids bind selectively with high affinity to a galectin-8 N-terminal domain
Pal, Kumar Bhaskar,Mahanti, Mukul,Huang, Xiaoli,Persson, Stella,Sundin, Anders P.,Zetterberg, Fredrik R.,Oredsson, Stina,Leffler, Hakon,Nilsson, Ulf J.
, p. 6295 - 6305 (2018/09/10)
Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside. Molecular dynamics simulations proposed an interaction mode in which Arg59 had moved 2.5 ? and in which an inhibitor carboxylate and quinoline nitrogen formed structure-stabilizing water-mediated hydrogen bonds. The compounds were demonstrated to be non-toxic in an MTT assay with several breast cancer cell lines and one normal cell line. The improved affinity, selectivity, and low cytotoxicity suggest that the quinoline-galactoside derivatives provide an attractive starting point for the development of galectin-8N inhibitors potentially interfering with pathological lymphangiogenesis, autophagy, and tumor progression.
NEW TRICYCLIC DERIVATIVES AS LTD4 ANTAGONISTS
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Page 42, (2008/06/13)
Compounds of formula (I) and their pharmaceutically acceptable salts are provided as well as processes for the manufacture of such compounds. The compounds are useful in the treatment or prevention of inflammatory and allergic diseases.