Synthetic modification of protein surfaces to mediate induced-proximity pharmacology
Lyn H Jones1,2
1Center for Protein Degradation, Dana-Farber Cancer Institute 360 Longwood Avenue Boston MA USA.
Abstract:
Molecular glues and bifunctional small molecules, such as targeted protein degraders, induce protein proximity to mediate gain-of-function pharmacology. Emerging technologies that synthetically manipulate protein surfaces to create neoproteins, and the development of covalent chemical probes for intra- and inter-protein surface labeling are described. Ligand-directed protein surface modification strategies have the potential to enhance the induced-proximity pharmacology toolkit and expand the druggable proteome, and this Opinion considers the opportunities and challenges that lie ahead.
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