Research Projects

Precision engineering of proteins has been a long-standing goal in healthcare, with recent growth in protein-based therapeutics highlighting the need for robust chemical platforms. However, the complex functional group composition in native proteins has hindered the field's growth. However, a systematic effort to understand the principles for simultaneous regulation of reactivity and selectivity has provided exciting insights. Methods have been developed to precisely target reactivity hotspots in proteins, with the potential of multistep pathways involving reversible generation of imine and site-selective modification of His, Lys, and Asp. These methods emphasize the importance of understanding core principles to deliver comprehensive protein engineering platforms at the chemistry-biology-medicine interface. A DisINtegrate or DIN theory has been evolving in the group, arguing that multi-step chemical processes can create a unique opportunity to segregate challenges of precise bioconjugation and solve them separately. The project aims to establish the ground principles for precise and modular chemical methods to cover the landscape beyond protein-defined reactivity order.