Engineered cystine-knot miniproteins for diagnostic applications

Owing to their extraordinary thermal and biological stability, cystine-knot miniproteins provide an attractive scaffold for the development of peptide-based diagnostics. One of the major advantages of this scaffold lies in the fact that the disulfide-constrained structural core can be functionalized by decoration with bioactive-loop residues. Methods have been developed to generate miniproteins with prescribed binding characteristics to a broad spectrum of different target proteins. They combine structural, biophysical and functional features that are beneficial for applications in molecular diagnostics in vivo (i.e., high affinity and selectivity, small size, high biological stability and fast renal clearance). Promising candidates for tumor imaging have been generated recently and evaluated in animal models, and more applications are expected in the near future.