11 Since Hsp90 is responsible for the folding of oncogenic proteins, its inhibition by a CTPR390 variant with higher affinity (1 M) resulted in the reduction of HER2 protein production, responsible for. An overview will be provided about the current approaches, and some emerging trends will be identified. Among the CTPR designed binders, CTPR390 is an antibody-mimetic protein built on a three block CTPR scaffold (15 kDa) in which several mutations enabled binding to the C-terminal region of the eukaryotic chaperone Hsp90 with moderate affinity (200 M) but high specificity, inhibiting it.
ENGINEERED PROTEIN SCAFFOLD INHIBITOR HOW TO
This review will therefore concentrate on the critical description of the structural properties of experimentally tested protein scaffolds and of the novel functions that have been achieved on their basis, rather than on the methodology of how to best select a particular mutant with a certain activity. There are many protease inhibitors in nature. However, it appears that not all kinds of polypeptide fold which may appear attractive for the engineering of loop regions at a first glance will indeed permit the construction of independent ligand-binding sites with high affinities and specificities. Abstract: Proteases are one of attractive therapeutic targets to play key roles in pharmacological action. Recently, the scaffold concept has even been adopted for the construction of enzymes. Hence, among others, single domains of antibodies or of the immunoglobulin superfamily, protease inhibitors, helix-bundle proteins, disulphide-knotted peptides and lipocalins were investigated. Protein engineering, the prerequisite for the advent of all. Properties like small size of the receptor protein, stability and ease of production were the focus of this work. Engineered protein display scaffolds, when specifically selected, can bind virtually to any target. After the application of antibody engineering methods along with library techniques had resulted in first successes in the selection of functional antibody fragments, several laboratories began to exploit other types of protein architectures for the construction of practically useful binding proteins. This development started with the notion that immunoglobulins owe their function to the composition of a conserved framework region and a spatially well-defined antigen-binding site made of peptide segments that are hypervariable both in sequence and in conformation. The use of so-called protein scaffolds has recently attracted considerable attention in biochemistry in the context of generating novel types of ligand receptors for various applications in research and medicine.