UC Irvine

Abstract 1:Synthetic routes to a heterobifunctional cysteine-lysine linker (MSSO) and an alkyne-bearing photo-inducible non-specific cross-linker (DzYSO) were developed and executed to provide collision-induced dissociation (CID) cleavable cross-linkers to probe protein structural dynamics. Additionally, an alkynylated acid-cleavable cross-linker (Alkyne-A-DIA) was designed and synthesized to evaluate potential for use of a ketal in selectively releasing biotinylated cross-linked fragments. The three linkers will be used for in vitro and in vivo protein interaction elucidation studies analyzed through liquid chromatography tandem mass spectrometry. Abstract 2: p53 is an enzyme that is responsible for facilitating cell cycle arrest, DNA repair, and apoptosis. It has been linked extensively to the development of cancer upon the introduction of missense mutations to structurally integral amino acids. Benzoimidazolylphenylpropenones and indolylphenylpropenones have shown promise in the restoration of native structure and function to mutant forms of p53 (R175, Y220C, R248W, R273H, G245S and R280Q) resulting in cytotoxic activity against cancerous cell lines possessing these mutations. These substrates were synthesized to reactivate p53 and photo-label the binding site targeted by these compounds. Abstract 3: The synthesis of intermediates toward ent-kaurane diterpenoid crokonoid A is discussed. In this discussion, the logic behind our approach and the optimization of several steps in the sequence are explored. Preliminary experiments to probe how to effectively set and maintain the stereocenter at C-14 are reported, without much success thus far.