The goal of this project was to synthesize a library of D and L- amino acid chemical probes to investigate how chirality impacts the specificity of their binding to reactive cysteine residues in breast cancer cell lysates. Chemical probes can be designed to interact specifically with protein’s reactive amino acid residues and may be used to study the role of functional amino acids. Cysteine residues are the least abundantly incorporated in the human proteome and have an array of functions including co-factor binding, structure stabilization, signaling, and protein activation. This project involved the facile synthesis of a library of chiral probes using D and L-amino acid scaffold to investigate cysteine-mediated protein activities associated with estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer. The L-amino acid library with a complementary D-amino acid library will allow for investigation of how chirality affects the binding specificity for unique cysteine residues. The probes have three functional groups including: (1) an electrophile to covalently modify cysteine residues, (2) an alkyne handle for visualization of modified proteins, and (3) a directing group for targeting specific proteins of interest. The probes will be evaluated in ER/PR positive breast cancer cell line, MCF7. A greater understanding of the mechanisms causing breast cancer will be obtained by developing a unique library of probes to study novel cysteine-mediated protein activities. The protein targets identified can also serve as potential drug targets to be used in the treatment of breast cancer.

Synthesis of a tri-functional, cysteine specific D and L-amino acid probe library to investigate the effects of probe chirality on protein selectivity in breast cancer cells

2019 Spring National Meeting

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