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Type: Journal article
Title: The key position: influence of staple location on constrained peptide conformation and binding
Author: Keeling, K.
Cho, O.
Scanlon, D.
Booker, G.
Abell, A.
Wegener, K.
Citation: Organic & Biomolecular Chemistry, 2016; 14(41):9731-9735
Publisher: The Royal Society of Chemistry
Issue Date: 2016
ISSN: 1477-0520
Statement of
Kelly L. Keeling, Okki Cho, Denis B. Scanlon, Grant W. Booker, Andrew D. Abell and Kate L. Wegener
Abstract: Constrained α-helical peptides are showing potential as biological probes and therapeutic agents that target protein-protein interactions. However, the factors that determine the optimal constraint locations are still largely unknown. Using the β-integrin/talin protein interaction as a model system, we examine the effect of constraint location on helical conformation, as well as binding affinity, using circular dichroism and NMR spectroscopy. Stapling increased the overall helical content of each integrin-based peptide tested. However, NMR analysis revealed that different regions within the peptide are stabilised, depending on constraint location, and that these differences correlate with the changes observed in talin binding mode and affinity. In addition, we show that examination of the atomic structure of the parent peptide provides insight into the appropriate placement of helical constraints.
Keywords: Lactams; Peptide Fragments; Talin; Integrin beta3; Amino Acid Sequence; Protein Structure, Secondary; Protein Binding; Models, Molecular; Proteolysis
Description: First published online 29 Sep 2016
Rights: This journal is © The Royal Society of Chemistry 2016
RMID: 0030056611
DOI: 10.1039/c6ob01745b
Grant ID:
Appears in Collections:Molecular and Biomedical Science publications

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