title: A novel strategy to design binding molecules harnessing the modular nature of repeat proteins.
abstract: Repeat proteins, such as ankyrin or leucine-rich repeat proteins, are ubiquitous binding molecules, which occur, unlike antibodies, intra- and extracellularly. Their unique modular architecture features repeating structural units (repeats), which stack together to form elongated repeat domains displaying variable and modular target-binding surfaces. Based on this modularity, we developed a novel strategy to generate combinatorial libraries of polypeptides with highly diversified binding specificities. This strategy includes the consensus design of self-compatible repeats displaying variable surface residues and their random assembly into repeat domains. We envision that such repeat protein libraries will be highly valuable sources for novel binding molecules especially suitable for intracellular applications.
authors.affiliation: Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Patrik
authors.initials: P
authors.lastname: Forrer
authors.forename: Michael T
authors.initials: MT
authors.lastname: Stumpp
authors.forename: H Kaspar
authors.initials: HK
authors.lastname: Binz
authors.forename: Andreas
authors.initials: A
authors.lastname: Plückthun
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008969:Molecular Sequence Data; D019151:Peptide Library; D011487:Protein Conformation; D015202:Protein Engineering; D020449:Repetitive Sequences, Amino Acid
chemical_list: D019151:Peptide Library