N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

Discovering New Classes of Brugia malayi Asparaginyl-tRNA Synthetase Inhibitors and Relating Specificity to Conformational Change

“…Lee and Kim used comparative molecular field analysis [81] to dock four known inhibitors of S. aureus MetRS and develop a predictive quantitative structureactivity relationship [82]. Most of the highly potent and selective AARS inhibitors discovered in recent years have come from in vitro screening and optimization studies [83][84][85][86]. Here we show that structure-based screening against an AARS target can identify several new classes of inhibitors.…”

Siderophore Biosynthesis Inhibitors

“…The acylsulfamate linkage, inspired from the natural product ascamycin 11 [28] has been extensively employed as a stable bioisostere of the labile acylphosphate linkage for the development of aaRS inhibitors (Figure 14.5) [29][30][31][32][33][34][35][36]. These inhibitors typically provide potent inhibition of the corresponding aaRSs.…”

“…Observations with related bisubstrate inhibitors developed for aminoacyl tRNA synthetases has shown that the linker region is very sensitive to modification [25,26]. Attempts to either increase [35] or decrease [42] the length reduced potency dramatically. Thus, most analogues investigated have maintained the native linker spacing, but explored modifications to the both the molecular geometry and polarity of the linker pharmacophore.…”

Targeting methionyl tRNA synthetase: design, synthesis and antibacterial activity against Clostridium difficile of novel 3-biaryl-N-benzylpropan-1-amine derivatives

“…These inhibitors are divided into either adenosine or non-adenosine analogues. Adenosine analogues (Figure 1) are thought to mimic the high-energy intermediate aminoacyl-AMP, thus blocking the aaRS pocket 7 . Non-adenosine analogues may have vast structural differences compared with the natural substrate aminoacyl-AMP, but they still have good enzyme inhibitory activity.…”