Engineering of Repeat Proteins as Novel Scaffolds of Selective Binding

Pluecki2

Over the last few years, we have developed an alternative to antibodies, which can be generated as specific binding proteins: repeat proteins. Repeat proteins are next to antibodies the most common class of binding proteins found in nature. By using consensus engineering, libraries of repeat proteins have been designed from which specific, high-affinity binding proteins can be selected.

Why are they interesting? They are very stable and do not have disulfide bonds and therefore, unlike most antibodies, also work inside the cell. They can be prepared in very large amounts from E. coli, and show affinities up to the picomolar range.

What can you do with them? They are being developed in the research group as tumor targeting reagents, as intracellular inhibitors to study signaling inside the cell, for co-crystallization of membrane proteins, and as model proteins to study fundamental questions of protein folding and design.

Most of the work carried out in the past concentrated on Designed Ankyrin Repeat Proteins (DARPins), but other classes have now been constructed, especially to design a general solution to the sequence-specific binding or peptides.