The alarming increase in bacterial resistance over the last decade, coupled with the lack of new classes of antibiotics to treat resistant infections, is a growing healthcare threat. In continued efforts to develop new potent antimicrobial agents, a novel class of acrylic esters was synthesized. To determine the molecular target for this class of compounds, the novel alkyne TI-I-100 was designed as a substrate for the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). Gratifyingly, TI-I-100 exhibited promising MIC values of 0.25-4.0 µg/mL against clinically significant antibiotic-resistant strains such as MRSA, MDR VISA, and VRE. Consequently, this stimulated the search for the molecular target employing the CuAAC reaction using the Click-iT Plus Alexa Fluor Picolyl Azide Toolkit with fluorescently tagged Alexa Fluor 647 picolyl azide (AF647) within Staphylococcus aureus lysate.  This permitted experiments to identify <i>S. aureus</i> proteins that had been covalently modified by the alkyne, TI-I-100 to be seen on SDS-PAGE under fluorescence. Encouraged by the results, AF647 was replaced with biotin azide in order to isolate the targeted proteins using streptavidin beads. Later, the purified protein fractions were subjected to peptide mass fingerprinting for protein identification and results will be presented.

Identifying of the molecular target for the potent antimicrobial agent TI-I-100 to treat drug resistance bacteria

2019 Spring National Meeting

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