engineered protein scaffold inhibitor therapeutics

The advantage of focused screens with conformationally-defined protein scaffolds is that conservation of the geometry of the natural binding epitopes may preserve binding site specificity while allowing direct mimicry by various synthetic secondary structure scaffolds. Engineered proteins displaying conformationally-defined epitopes may serve as attractive alternatives to natural protein partners as they can be strictly screened for tight binding. The mimics typically need to be optimized for potency. However, direct mimicry often does not lead to high affinity ligands because the natural complexes themselves are functionally transient and of low affinity. Possibilities of engineered protein scaffolds have been explored in research, diagnostics and therapy in the last few years. Many alternative scaffolds contain homogenous secondary structure that helps stabilize the protein. Gastric inhibitory polypeptide receptor (GIPR) plays a role in regulation of. Rationally designed protein-protein interaction inhibitors mimic interfacial binding epitopes, specifically residues that contribute significantly to binding. The chapter presents considerations for the development and application of alternative scaffolds as next-generation engineered protein therapeutics. Yuan Cheng, PhD, Senior Principal Scientist, Therapeutic Discovery, Amgen, Inc.

Engineered protein scaffold inhibitor therapeutics