“CovCore” covalently constrained mesosized protein work published
See the collaborative work of the DeGrado lab and David Baker's group (University of Washington) published online for early access in the Proceedings of the National Academies of Sciences. Congrats to co-first authors Bobo Dang and Haifan Wu.
Therapeutics on the market today mainly fall into two distinct classes: small molecules and antibodies (more complex and ~100-200 times larger). This work presents a novel class of de novo designed protein therapeutics intermediate in size and complexity, whose structure is held together primarily by covalent modification. Given their size and thiol-based modification, the proteins are not only amenable to chemical synthesis, but can also be produced biologically as part of artificial affinity maturation screens, e.g. to develop as inhibitors of protein interactions.
The DeGrado lab and others are excited to explore the utility of these types of covalently constrained mini-proteins in the research lab and in the clinic in the upcoming years!