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The Complete Assessment of Small Molecule and Peptidomimetic Inhibitors of Sortase A Towards Antivirulence Treatment.
Chemistry : a European Journal 2024 May 9
This review covers the most recent advances in the development of inhibitors for the bacterial enzyme sortase A (SrtA). Sortase A (SrtA) is a critical virulence factor present ubiquitously in Gram-positive bacteria of which many are considered pathogenic. Sortases are key enzymes regulating bacterial adherence to host cells, by anchoring extracellular matrix-binding proteins to the bacterial outer cell wall. By targeting virulence factors, effective treatment can be achieved, without inducing antibiotic resistance to the treatment. All in all, this would lead to a more sustainable, long-term approach to treating bacterial infections, including ones that display multiple resistance to current therapeutics. Currently, it appears there are many promising approaches available that have the potential to advance into further clinical development, with peptidomimetic and in vivo active small molecules among the most promising. There are currently no approved drugs on the market targeting SrtA, despite its promise, adding to the relevance of this review article, as it extends to the pharmaceutical industry additionally to academic researchers.
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