DARPin
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DARPins (an acronym for designed ankyrin repeat proteins) are genetically engineered antibody mimetic proteins typically exhibiting highly specific and high-affinity target protein binding. They are derived from natural ankyrin repeat proteins, one of the most common classes of binding proteins in nature, which are responsible for diverse functions such as cell signaling, regulation and structural integrity of the cell. DARPins consist of at least three, repeat motifs or modules, of which the most N- and the most C-terminal modules are referred to as "caps", since they shield the hydrophobic core of the protein. The number of internal modules is indicated as number (e.g. N1C, N2C, N3C, ...) while the caps are indicated with "N" or "C", respectively. The molecular mass of e.g. 14 or 18 kDa (kilodaltons) for four- (N2C) or five- (N3C) repeat DARPins is rather small for a biologic (ca 10% of the size of an IgG).
DARPins constitute a new class of potent, specific and versatile small-protein therapeutics, and are used as investigational tools in various research, diagnostic and therapeutic applications.[1] Molecular Partners AG, a clinical-stage biopharmaceutical company with several DARPin molecules in clinical and preclinical development, is currently pursuing development of therapeutic DARPins both through their own development and in parallel with partners. Athebio AG builds on further improving the DARPin scaffold for a partnering model approach.[2]
In addition, DARPins can be used as crystallization chaperones for soluble and membrane proteins, including G protein-coupled receptors (GPCRs), either as binding partners or as rigid fusions to the target protein, a concept now being extended to structure determination by cryoEM.[3][4][5][6]