1. Photoactivated 1,3-Dipolar Cycloaddition: Scope and Applications
A mild, photoactivated 1,3-dipolar cycloaddition procedure was developed. This procedure involves the in situ generation of the reactive nitrileimine dipoles using a hand-held UV lamp at 302 nm, followed by spontaneous cycloaddition with a broad range of 1,3-dipolarophiles with excellent solvent compatibility, functional group tolerance, regioselectivity, and yield.
Dr. Lin’s group is primarily interested in developing and applying new chemical tools to understand protein dynamics and function in living systems. One of the ongoing projects aims to develop a battery of photo-inducible bioorthogonal reactions―reactions that can be carried out in aqueous media under physiological conditions―and apply them to in vivo protein modification as well as target-guided synthesis of protein inhibitors, e.g. MDM2 inhibitors with potential anti-cancer activities. Another project focuses on the synthesis of novel small-molecule substrates and inhibitors of the ubiquitination pathway, a central biochemical pathway regulating in a wide array of biological processes such as signal transduction, cell division, and immune response. These chemical tools can not only be employed to study the mechanism of this critical biochemical pathway but also be further developed into anti-cancer drugs.
A robust, bioorthogonal 1,3-dipolar cycloaddition has been used for fast and selective protein modification