A new bio-orthogonal strategy, termed ‘catch and release’, to battle bacterial infections will be presented. The approach is based on recent developments of the inverse electron demand Diels-Alder (IEDDA) reaction that allows release of therapeutic payloads attached to the trans-cyclooctene group after the initial cycloaddition step. The strategy starts with the injection of the biocompatible hydrogel modified with tetrazine near the site of the infection. An antibiotic with attenuated activity containing a releasable trans-cyclooctene moiety (pro-drug) is injected intravenously and travels through the circulatory system. When the pro-drug and the hydrogel come near, the bio-orthogonal agents react with each other through IEDDA reaction localizing the therapeutic payload. The multivalency of the hydrogel’s surface provides a large number of tetrazine groups capable of ‘catching’ the systemically administered antibiotic pro-drug. Finally, the resulting intermediate isomerizes spontaneously releasing the active antibiotic from the hydrogel to perform its therapeutic function locally. Evaluation of the ‘catch and release’ strategy in standard laboratory strains, Staphylococcus aureus (Staph.auresus) methicillin resistant (MRSA) and Staphyloccocus aureus methicillin sensitive (MSSA) will be described.

Catch and release strategy to treat bacterial infections

254th National Meeting (2017)

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