Abstract: Nature regulates many biological processes through post-translational modifications that modify protein activity and relay signals through protein networks. Interpretation of how nature uses these modifications will provide new insights to biological regulation, and open new frontiers in the design of therapeutic modalities that mimic nature to treat human disease.

Abstract: Protein-protein complexes are difficult targets for inhibitor design, and therefore, offer a testing ground for new approaches.  We are developing a rational design approach that begins by mimicry of protein interfaces by constrained peptides and peptidomimetics.  However, direct mimicry of protein interfaces often leads to weak inhibitors.  We overcome this inherent limitation by designing nonnatural side chain functionality.  The first part of this presentation will discuss the application of our approach to the discovery of inhibitors f

Abstract: The STING pathway is an essential innate immune pathway that is activated when double stranded DNA is detected in the cytosol. This occurs during viral infection and tumorigenesis and activation of the pathway elicits strong anti-viral and anti-cancer immunity. However, double stranded DNA is also misplaced in the cytosol during trauma, radiation, autoimmune syndromes, and aging. In these cases, STING activation exacerbates the unwanted immunity against healthy tissues.

Abstract: Biologically active alkaloids continue to serve as a means of biomedical discovery in addition to serving as forcing functions for the invention of new chemical transformations. Structurally, many of these natural products and rationally designed drugs also contain one or more piperidine rings, making it the most common nitrogenous heterocycle amongst approved therapeutics. Thus, the concise redox-economic construction of these heterocycles in the context of target-oriented synthesis has become a recent research focus in our lab.

This lecture will cover recent achievements in the discovery, protein engineering and application of enzymes in biocatalysis [1]. For the asymmetric synthesis of chiral amines, we created (S)-selective amine transaminases for the acceptance of bulky ketones [2]. Most recently, we have developed a sophisticated growth selection method and could create highly active and selective enzymes from three classes to make important chiral precursors for pharmaceutical building blocks [3]. We have also explored machine learning to guide enzyme engineering of transaminases [4].