Photons have multiple enabling advantages to control chemical reactions and stimuli-responsive materials. In this seminar, I will discuss our groups effort to design and develop a new class of negative photochromic molecules termed DASA, their incorporation into materials and subsequent effort to unlock their potential to convert light directly into mechanical work. Additionally, a new Diels–Alder based photoclick platform to enable bio-orthogonal chemistry with spatial control for biomaterial applications will be discussed.
Abstract: KRAS is one of the most frequently mutated oncogenes in human cancer. Despite more than three decades of research, indirect approaches targeting KRAS-mutant cancers have largely failed to show clinical benefit, and direct approaches have been stymied by the apparently ‘undruggable’ nature of KRAS. I’ll describe efforts at Amgen to identify cysteine-reactive molecules capable of selectively inhibiting a prevalent KRAS mutation, KRASG12C. These efforts leveraged iterative screening and structural biology studies, property-based optimization, and
Polymers are arguably the most important materials on Earth. Despite a century of study, however, much remains unknown about how the molecular-scale features of polymers translate to bulk properties, preventing predictive design of next-generation materials. This talk will highlight our efforts to install cleavable bonds into precise locations within macromolecules, showing how we can use selective bond cleavage to unveil previously hidden features of polymer structure and enable new material functions.
Abstract: The selective generation and controlled reactivity of open-shell reactive species continues to serve as inspiration for new reaction development in chemical synthesis. This talk will describe recent advances using phosphorous-based reagents to generate carbon- and heteroatom-centered radicals via sequential atom-transfer radical additions as well as the use of copper compounds engaged in light-mediated metal-ligand co-operativity to harness and activate non-conjugated alkenes towards photocycloadditions.
Process safety is a critical function within the pharmaceutical industry to ensure safety when performing reactions. An overview of how we approach process safety and a case study to demonstrate the application of our approach to a Barbier-type Grignard reaction in the synthesis of Kyprolis will be presented.
Abstract: RNA transcribed from the genome in the nucleus bears little resemblance to the RNA polymer it will ultimately become in the cytoplasm where it is translated into protein. Well-known processes such as capping, splicing and polyadenylation, as well as the recently discovered and ever-expanding list of diverse chemical modifications and editing, significantly alter the properties and fates of a given RNA during the course of its lifetime. These alterations regulate critical aspects of RNA function such as stability, transport, protein binding, and translation.