Related Products of 705-86-2, As an important bridge between the micro and macro material world, chemistry is one of the main methods and means for humans to understand and transform the material world. 705-86-2, Name is 6-Pentyltetrahydro-2H-pyran-2-one, SMILES is O=C1CCCC(CCCCC)O1, belongs to Triazoles compound. In a article, author is De Ruysscher, Dries, introduce new discover of the category.
Synthesis and structure-activity studies of novel anhydrohexitol- based Leucyl-tRNA synthetase inhibitors
Leucyl-tRNA synthetase (LeuRS) is a clinically validated target for the development of antimicrobials. This enzyme catalyzes the formation of charged tRNA(Leu) molecules, an essential substrate for protein translation. In the first step of catalysis LeuRS activates leucine using ATP, forming a leucyl-adenylate intermediate. Bi-substrate inhibitors that mimic this chemically labile phosphoanhydride-linked nucleoside have proven to be potent inhibitors of different members of the aminoacyl-tRNA synthetase family but, to date, they have demonstrated poor antibacterial activity. We synthesized a small series of 1,5-anhydrohexitol-based analogues coupled to a variety of triazoles and performed detailed structureactivity relationship studies with bacterial LeuRS. In an in vitro assay, K-i(app) values in the nanomolar range were demonstrated. Inhibitory activity differences between the compounds revealed that the polarity and size of the triazole substituents affect binding. X-ray crystallographic studies of N. gonorrhoeae LeuRS in complex with all the inhibitors highlighted the crucial interactions defining their relative enzyme inhibitory activities. We further examined their in vitro antimicrobial properties by screening against several bacterial and yeast strains. While only weak antibacterial activity against M. tuberculosis was detected, the extensive structural data which were obtained could make these LeuRS inhibitors a suitable starting point towards further antibiotic development. (C) 2020 Elsevier Masson SAS. All rights reserved.
Related Products of 705-86-2, Each elementary reaction can be described in terms of its molecularity, the number of molecules that collide in that step. The slowest step in a reaction mechanism is the rate-determining step.you can also check out more blogs about 705-86-2.