title: Conversion of low-affinity peptides to high-affinity peptide binders by using a β-hairpin scaffold-assisted approach.
abstract: Affinity maturation of protein-targeting peptides is generally accomplished by homo- or heterodimerization of known peptides. However, applying a heterodimerization approach is difficult because it is not clear a priori what length or type of linker is required for cooperative binding to a target. Thus, an efficient and simple affinity maturation method for converting low-affinity peptides into high-affinity peptides would clearly be advantageous for advancing peptide-based therapeutics. Here, we describe the development of a novel affinity maturation method based on a robust β-hairpin scaffold and combinatorial phage-display technology. With this strategy, we were able to increase the affinity of existing peptides by more than four orders of magnitude. Taken together, our data demonstrate that this scaffold-assisted approach is highly efficient and effective in generating high-affinity peptides from their low-affinity counterparts.
authors.affiliation: Korea Institute of Ceramic Engineering and Technology, Seoul 153-801 (South Korea).
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: Yonghyun
authors.initials: Y
authors.lastname: Lee
authors.forename: Hyungsu
authors.initials: H
authors.lastname: Jeon
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D019151:Peptide Library; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006657:Histones; D019151:Peptide Library; D005047:Etoposide
keywords: affinity maturation; aptides; beta-hairpin scaffold; peptides; phage display; surface plasmon resonance