Here we review different classes of engineered proteins for their binding epitope geometry and as leads for synthetic secondary and tertiary structure mimics.Ĭopyright © 2018 Elsevier Ltd. 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. More than 120 different SH2 domains exist in the human proteome, and taking advantage of their natural affinity for pTyr-motif SH2 domains has been well-characterized and used to probe pTyr proteins from cell or tissue lysates in a high-throughput microarray format (5, 6). 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 unbiased profiling of pTyr protein complexes in tumor samples is challenging and rarely reported. The mimics typically need to be optimized for potency. This editorial describes how the Affibody® platform, a novel protein targeting scaffold, could be utilized to develop C5 inhibitors for versatile and efficient therapeutic targeting of the terminal complement pathway. However, direct mimicry often does not lead to high affinity ligands because the natural complexes themselves are functionally transient and of low affinity. 11:50 Antibody-Targeted Superantigens and Antibody Directed Enzyme Prodrug Therapy for Improved. Many protein based therapeutics, vaccines, and scaffolds with greater safety. Rationally designed protein-protein interaction inhibitors mimic interfacial binding epitopes, specifically residues that contribute significantly to binding. Engineering, development and clinical data will be presented. The fascinating field of protein engineering has provided breakthroughs by producing plethora of specifically engineered/rationally designed proteins with different functionalities and wide-scale applications in industrial, biotechnological, and pharmaceutical sectors.
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