Lindsey-Crosthwait, A, Rodriguez-Lema, D, Walko, M orcid.org/0000-0002-7160-6136 et al. (2 more authors) (2021) Structural optimization of reversible dibromomaleimide peptide stapling. Peptide Science, 113 (1). e24157. ISSN 2475-8817
Abstract
Methods to constrain peptides in a bioactive α-helical conformation for inhibition of protein-protein interactions represent an ongoing area of investigation in chemical biology. Recently, the first example of a reversible “stapling” methodology was described which exploits native cysteine or homocysteine residues spaced at the i and i + 4 positions in a peptide sequence together with the thiol selective reactivity of dibromomaleimides (a previous study). This manuscript reports on the optimization of the maleimide based constraint, focusing on the kinetics of macrocyclization and the extent to which helicity is promoted with different thiol containing amino acids. The study identified an optimal stapling combination of X₁ = L-Cys and X₅ = L-hCys in the context of the model peptide Ac-X₁AAAX₅-NH₂, which should prove useful in implementing the dibromomaleimide stapling strategy in peptidomimetic ligand discovery programmes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Peptide Science published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | constrained peptides; dibromomaleimide; peptide conformation; protein‐protein interactions |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Inorganic Chemistry (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Mar 2020 12:29 |
Last Modified: | 25 Jun 2023 22:11 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/pep2.24157 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158005 |
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