Abstract
Peptide display approaches, in which peptide epitopes of known binding activities are grafted onto stable protein scaffolds, have been developed to constrain the peptide in its bioactive conformation and to enhance its stability. However, peptide grafting can be a lengthy process requiring extensive computational modeling and/or optimisation by directed evolution techniques. In this study, we show that ultra-stable consensus-designed tetratricopeptide repeat (CTPR) proteins are amenable to the grafting of peptides that bind the Kelch-like ECH-associated protein 1 (Keap1) onto the loop between adjacent repeats. We explore simple strategies to optimize the grafting process and show that modest improvements in Keap1-binding affinity can be obtained by changing the composition of the linker sequence flanking either side of the binding peptide.
Original language | English |
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Pages (from-to) | 738-745 |
Number of pages | 8 |
Journal | Protein Science |
Volume | 28 |
Issue number | 4 |
Early online date | 11 Feb 2019 |
DOIs | |
Publication status | Published - 1 Apr 2019 |
Bibliographical note
© 2019 The Protein Society.Keywords
- biologics
- protein engineering
- protein–protein interaction
- repeat protein
- tetratricopeptide repeat
- therapeutics
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology