Rullo Lab Reveals How Target Binding Accelerates Covalent Drug Reactions

Congratulations to the Rullo lab on their recent publication in ACS Central Science, titled “Target Binding Accelerates Covalent Drug Reaction Kinetics via a Proximity-Controlled Mechanism” (DOI: 10.1021/acscentsci.5c00699).

Covalent drugs have the unique ability to chemically and potentially irreversibly attach to their target receptor of interest. This can confer significant therapeutic advantages wlth respect to drug potency and efficacy if the covalent reaction selectivity can be predicted and controlled. This publication from the Rullo lab used physical organic chemistry approaches to elucidate a unique property of the reactive electrophile within the drug that enables for “turn on” or “latent” reactivity only when it engages the intended target of interest. This can enable for enhanced control over the kinetics and selectively of covalent drugs and allows for the use of readily acccessible lower affinity binding ligands like peptides and carbohydrates for covalent drug development  across diverse disease indications.

Read the full article in ACS Central Science