Designed Repeat Proteins

All repeat proteins share a modular architecture: A single structural motif occurs several times and stacks together to form an elongated repeat domain. By analysis of thousands of sequences and high resolution structures of a natural repeat protein family, an idealized repeat module (consensus module) was deduced in a process termed consensus design.
Using this strategy, several sites within such a consensus module were identified, which allow the introduction of sequence diversity. These idealized and diversity carrying repeat modules are the basic building block for the assembly of combinatorial designed repeat protein libraries (DRP libraries). Since the number of repeat modules in a designed repeat protein is not fixed, the binding site is adjustable in size and can always be increased by incorporation of additional repeat modules. Likewise, the modular architecture of repeat proteins allows unique opportunities for affinity maturation and modification existing binders, such as shuffling of the binding site.
To date, several DRP libraries of several classes of repeat proteins have been constructed and hundreds of specifically binding repeat proteins to diverse protein targets have been selected from these libraries. The technically most advanced DRP library is based on natural ankyrin repeat proteins, and is termed Designed Ankyrin Repeat Protein (DARPin) library.