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NOTE: Representational structure depicted, where ‘X’
represents the corresponding amino acid.
Aminoacyl adenylate analogs (5’-O-[N-(L-aminoacyl)sulfamoyl]adenosines) function as potent inhibitors of the aminoacyl-tRNA synthetase enzymes. tRNA synthetases play vital roles in translation as they are responsible for transferring the correct amino acid to their corresponding tRNA. Analogs of the aminoacyl intermediates have been used in structural and mechanistic studies of the enzymes, uncovering their evolutionary history, and determining the extent of amino acid discrimination exhibited by each synthetase.
More recently, t-RNA synthetases have emerged as a potential platform for the development of new antibiotics that specifically target these enzymes as a way to inhibit bacterial growth. Modified aminoacyl adenosine analogs are also being used to evolve tRNA synthetases that can be used to incorporate modified amino acids into proteins, which are valuable for investigating structure-activity relationships or developing modified peptide based therapeutics. t-RNA synthetases from humans have also been found to possess cytokine activity and play a role in the regulation of angiogenesis.
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