Click Chemistry Reaction Development: Click chemistry is an approach to chemical synthesis conceived to enhance the construction of functional molecules, including new drugs, materials, and important chemical tools for biology. The Moses group focus on the development and application of novel click chemistry reactions, probing the reactivity of functional groups with unexplored “click” potential. As an example, the Moses group pioneered the first phosphorus-based click reaction, called Phosphorus Fluoride Exchange (PFEx), showcasing the power and orthogonality of this exciting new transformation.

Drug Derivatization: A fundamental goal of click chemistry is to accelerate the drug discovery process. The Moses laboratory has developed several array platforms that facilitate the rapid derivatization of complicated molecular scaffolds, including natural products and drug molecules. The goal? To identify lead compounds with improved therapeutic activity in combination with lower toxicity profiles in as little as two synthetic steps from the parent drug. By employing this approach, the Moses laboratory has identified numerous potent leads, including nanomolar microtubule targeting agents that engage the colchicine binding site of tubulin and antibiotic molecules with potent activity against drug-resistant bacteria.

Shapeshifting Drug Molecules: Traditionally, drug molecules are rigid molecules that interact with therapeutic targets via a “lock-in-key” mechanism. By employing the unique shapeshifting properties of bullvalene, the Moses lab is engineering an exciting new class of fluxional drug molecules, so-called “shapeshifting drugs,” that challenge this model of drug design. To date, this technology has been used to generate shapeshifting glycopeptide-containing dimers that evade the resistant mechanisms applied by Gram-positive bacteria to overcome vancomycin treatment (an antibiotic of last resort used to treat deadly MRSA).