Antibody-Drug Conjugates for Targeted Delivery of Antimicrobials

Antimicrobial prodrugs targeting bacterial enzymes can have high specificity and low off-target toxicity. Fluorescent probes can be used to identify bacterial strains susceptible to antimicrobial prodrugs. In the structure of these probes, a chemical trigger motif is coupled to a resorufin fluorophore. Five probes have been synthesised; three are intended to target bacterial nitroreductase, one targeting penicillin G amidase and the last one is intended to target beta-alanine aminopeptidase. The probes for nitroreductase use 4-nitrophenyl, 5-nitrofuranyl and 2-nitro-N-methyl-imidazolyl groups as a chemical trigger. The probes for penicillin amidase and beta-alanine aminopeptidase feature an amide that is attached to a benzene ring via the amide nitrogen. Synthesis of more amide-containing probes was attempted, where the amide nitrogen would be attached to a five-membered heterocycle. It was found that these probes are unstable and spontaneously self-immolate.