Developing Mycobacterium tuberculosis RecA Intein Splicing Inhibitors and Intein Splicing Inhibition Assay
Silberman, Julia Leah
2023
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The emergence of drug-resistant pathogens necessitates the development of new antimicrobial therapeutics. With the development of antibiotic resistance, Mycobacterium tuberculosis, the leading cause of death by a single infectious agent, has become more difficult to treat and thus more deadly. Inteins, intervening peptide sequences within some proteins, are a potential druggable target in tuberculosis ... read moreand other pathogens. They are only found in unicellular organisms, with a particularly high frequency in the essential housekeeping proteins of pathogenic microbes. Inteins must be spliced out through a self-catalytic process for the proteins to properly fold and function. Inhibition of this mechanism will thus also inhibit the function of these proteins essential to the survival and/or growth of the pathogen. This study investigates a strategy of electrophilic dual inhibitors for the Mycobacterium tuberculosis RecA intein. Warheads based on cysteine protease inhibitors have been synthesized, to be connected into bifunctional inhibitor constructs. In addition, this study details the development of an in vitro assay using intein-split green fluorescent protein to evaluate the efficacy of intein splicing inhibition
Thesis (B.S.)--Tufts University, 2023.
Submitted to the Dept. of Chemistry.
Advisor: Krishna Kumar.read less - ID:
- vx021v66f
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