UC San Diego

Chimeric small molecules offer a wide array of potential biologicalfunctionalties where metabolic pathways may be redirected towards noncognate substrates for applications in biological research and pharmaceutical development. Here we explore the design of a class of chimeric small molecules known as proteolysis targeting chimeras through structure-activity relationships (SARs), provide synthetic methodology to access PROTAC linker variants, and biologically evaluate a suite of human carbonic anhydrase II (hCAII) degrading chimeric small molecules through mammalian cell culture and western blotting techniques.