Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release
Name
Accepted Manuscript1.pdf
Description
Accepted version
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954.95 KB
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Author(s)
Pomplun, Sebastian Johannes
Shugrue, Christopher R.
Schmitt, Adeline M.
Schissel, Carly K.
Farquhar, Charlotte E.
Pentelute, Bradley L.
Date Issued
May 2020
Journal
Angewandte Chemie - International Edition
Publisher
Wiley
Citation
Pomplun, Sebastian et al. "Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release." Angewandte Chemie 59, 28 (May 2020): 11566-11572 © 2020 Wiley
Version
Author's final manuscript
Abstract
Capture and release of peptides is often a critical operation in the pathway to discovering materials with novel functions. However, the best methods for efficient capture impede facile release. To overcome this challenge, we report linkers based on secondary amino alcohols for the release of peptides after capture. These amino alcohols are based on serine (seramox) or isoserine (isoseramox) and can be incorporated into peptides during solid-phase peptide synthesis through reductive amination. Both linkers are quantitatively cleaved within minutes under NaIO4 treatment. Cleavage of isoseramox produced a native peptide N-terminus. This linker also showed broad substrate compatibility; incorporation into a synthetic peptide library resulted in the identification of all sequences by nanoLC-MS/MS. The linkers are cell compatible; a cell-penetrating peptide that contained this linker was efficiently captured and identified after uptake into cells. These findings suggest that such secondary amino alcohol based linkers might be suitable tools for peptide-discovery platforms.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1002/anie.202003478
