Development of covalent inhibitors for bacterial histidine kinases

开发细菌组氨酸激酶共价抑制剂

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Abstract

Antivirulence therapies offer an alternative strategy against antimicrobial resistance. We synthesized 2-aminobenzothiazole sulfonyl fluoride analogs for covalent histidine kinase inhibition. In vitro and in cellulo assays also identified lead inhibitors for affinity-based probe development. However, alkyne incorporation reduced bioactivity, emphasizing the challenges of designing functional probes while preserving inhibitor potency.

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