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).

In this study, the team used physical organic chemistry approaches to illuminate covalent drug reaction behaviour in response to target protein engagement. The group uncovers how and why the reaction kinetics of covalent drugs can be significantly enhanced by the binding interaction with a target receptor of interest, as a function of the electrophile reaction mechanism itself. This work contributes key insights into the molecular determinants that govern covalent drug selectivity and “reaction latency,” and will help guide the design of next-generation targeted covalent therapeutics.

Read the full article in ACS Central Science