In this episode, we're joined by Dr. Rai, who enlightens us about the exciting field of precision protein engineering and its potential applications.

Precision engineering of native proteins is akin to maintaining machinery – both necessitate an operational understanding and a robust set of tools for repair. Dr. Rai presents a technology that offers substantial control over various aspects of protein manipulation, including reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, and protein-selectivity. This technology is known as cysteine-based chemoselective Linchpin-Directed site-selective Modification of lysine residue in a protein (LDMC-K).

The strength of this user-friendly protocol lies in its ability to achieve quantitative conversions within an hour, leveraging chemically orthogonal C-S bond-formation and bond-dissociation. Interestingly, it offers the capacity to target a single lysine residue of a single protein in a complex biomolecular mixture, yielding an analytically pure single-site probe-engineered protein bioconjugate.

The LDMC-K technique also enables the creation of homogeneous antibody conjugates, which demonstrate highly selective anti-proliferative activity towards breast cancer cells.

Join us as we explore the depths of precision protein engineering, its implications, and its future prospects.

Key Words: Precision Protein Engineering, LDMC-K, Reactivity, Chemoselectivity, Site-selectivity, Protein-selectivity, Breast Cancer, Antibody Conjugates.

Reddy, N.C., Molla, R., Joshi, P.N. et al. Traceless cysteine-linchpin enables precision engineering of lysine in native proteins. Nat Commun (2022). https://doi.org/10.1038/s41467-022-33772-1