Category: esters-buliding-blocksIn 2019 ,《Thienopyrimidinone Derivatives That Inhibit Bacterial tRNA (Guanine37-N1)-Methyltransferase (TrmD) by Restructuring the Active Site with a Tyrosine-Flipping Mechanism》 was published in Journal of Medicinal Chemistry. The article was written by Zhong, Wenhe; Pasunooti, Kalyan Kumar; Balamkundu, Seetharamsing; Wong, Yee Hwa; Nah, Qianhui; Gadi, Vinod; Gnanakalai, Shanmugavel; Chionh, Yok Hian; McBee, Megan E.; Gopal, Pooja; Lim, Siau Hoi; Olivier, Nelson; Buurman, Ed T.; Dick, Thomas; Liu, Chuan Fa; Lescar, Julien; Dedon, Peter C.. The article contains the following contents:
Among the >120 modified ribonucleosides in the prokaryotic epitranscriptome, many tRNA (tRNA) modifications are critical to bacterial survival, which makes their synthetic enzymes ideal targets for antibiotic development. Here we performed a structure-based design of inhibitors of tRNA-(N1G37) methyltransferase, TrmD, which is an essential enzyme in many bacterial pathogens. On the basis of crystal structures of TrmDs from Pseudomonas aeruginosa and Mycobacterium tuberculosis, we synthesized a series of thienopyrimidinone derivatives with nanomolar potency against TrmD in vitro and discovered a novel active site conformational change triggered by inhibitor binding. This tyrosine-flipping mechanism is unique found in P. aeruginosa TrmD and renders the enzyme inaccessible to the cofactor S-adenosyl-L-methionine (SAM) and probably to the substrate tRNA. Biophys. and biochem. structure-activity relationship studies provided insights into the mechanisms underlying the potency of thienopyrimidinones as TrmD inhibitors, with several derivatives found to be active against Gram-pos. and mycobacterial pathogens. These results lay a foundation for further development of TrmD inhibitors as antimicrobial agents. In the experiment, the researchers used tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3Category: esters-buliding-blocks)
Some of the reported applications of tert-Butyl (5-aminopentyl)carbamate(cas: 51644-96-3) include: synthesis of of a supermacrocycle that self-assemble to form organic nanotubes., preparation of water-soluble unsymmetrical sulforhodamine fluorophores from monobrominated sulfoxanthene dye, synthesis of functionalized porphyrins as biocompatible carrier system for photodynamic therapy (PDT).Category: esters-buliding-blocks
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