A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling
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Pentelute_A Perfluoroaryl.pdf
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Author(s)
Spokoyny, Alexander M.
Zou, Yekui
Yu, Hongtao
Lin, Yu-Shan
Pentelute, Bradley L.
Ling, Jingjing
Date Issued
April 2013
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Spokoyny, Alexander M., Yekui Zou, Jingjing J. Ling, Hongtao Yu, Yu-Shan Lin, and Bradley L. Pentelute. “ A Perfluoroaryl-Cysteine S[subscript N]Ar Chemistry Approach to Unprotected Peptide Stapling .” Journal of the American Chemical Society 135, no. 16 (April 24, 2013): 5946–5949.
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Author's final manuscript
Abstract
We report the discovery of a facile transformation between perfluoroaromatic molecules and a cysteine thiolate, which is arylated at room temperature. This new approach enabled us to selectively modify cysteine residues in unprotected peptides, providing access to variants containing rigid perfluoroaromatic staples. This stapling modification performed on a peptide sequence designed to bind the C-terminal domain of an HIV-1 capsid assembly polyprotein (C-CA) showed enhancement in binding, cell permeability, and proteolytic stability properties, as compared to the unstapled analog. Importantly, chemical stability of the formed staples allowed us to use this motif in the native chemical ligation-mediated synthesis of a small protein affibody that is capable of binding the human epidermal growth factor 2 receptor.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/ja400119t
