As an evolutionarily conserved enzyme family, silent information regulator 2 (Sir2) proteins catalyze post-translational NAD+-dependant lysine deacetylation reactions in critical cellular processes such as modulation of the meiotic checkpoint, transcriptional gene silencing and lifespan regulation. Sirtuin-6 (SIRT6), one of protein members in human sirtuin (Sir2) family, functions both NAD+-dependant lysine deacetylation and ADP-ribosylation reactions related to metabolism, gene silencing, and DNA repair. Therefore, targeting this class of proteins could be used as a therapeutic target for human diseases. This study presents the work toward developing a series of potential human SIRT6 protein lysine deacetylase inhibitors containing NƐ-thioacetyl-lysine (ThAcK).
The performance of polymer materials is not only related to their structures but also depends on their end groups, block size and balance of hydrophilic and hydrophobic segments. Mass spectrometry (MS) has emerged as a powerful tool for studying the microstructure of copolymers. Nevertheless, it is difficult to analyze a block copolymer that contains byproducts and impurities by using mass spectrometry alone. Coupling ultra pressure liquid chromatography (UPLC) with ion mobility mass spectrometry (IM-MS) on a Synapt HDMS mass spectrometer (UPLC-IM-MS) can facilitate the characterization of such complex mixtures containing structural isomers and isobaric compounds. This dissertation describes the new LC-IM-MS and LC-MS/MS approaches that can be employed to elucidate the composition and microstructure of a linear poly(styrene)-b-poly(ethylene oxide) block copolymer with cyclic byproducts and impurities.