Exploring new strategies for grafting binding peptides onto protein loops using a consensus-designed tetratricopeptide repeat scaffold

Sarah K Madden, Albert Perez-Riba, Laura S Itzhaki

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages738-745
Number of pages8
JournalProtein Science
Volume28
Issue number4
DOIs
StatusPublished - 11 Feb 2019

Cite this

Exploring new strategies for grafting binding peptides onto protein loops using a consensus-designed tetratricopeptide repeat scaffold. / Madden, Sarah K; Perez-Riba, Albert; Itzhaki, Laura S.

In: Protein Science, Vol. 28, No. 4, 11.02.2019, p. 738-745.

Research output: Contribution to journalArticle

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