Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release
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 peptid...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020
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| Online Access: | https://hdl.handle.net/1721.1/128119 |
| _version_ | 1826205316168024064 |
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| author | Pomplun, Sebastian Johannes Shugrue, Christopher R. Schmitt, Adeline M. Schissel, Carly K. Farquhar, Charlotte E. Pentelute, Bradley L. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Pomplun, Sebastian Johannes Shugrue, Christopher R. Schmitt, Adeline M. Schissel, Carly K. Farquhar, Charlotte E. Pentelute, Bradley L. |
| author_sort | Pomplun, Sebastian Johannes |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:10:45Z |
| format | Article |
| id | mit-1721.1/128119 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:10:45Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1281192022-10-01T13:34:02Z Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release Pomplun, Sebastian Johannes Shugrue, Christopher R. Schmitt, Adeline M. Schissel, Carly K. Farquhar, Charlotte E. Pentelute, Bradley L. Massachusetts Institute of Technology. Department of Chemistry 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. National Institutes of Health (Grants R01 GM110535, F32 GM133073) National Science Foundation (Grants 4000057398, 4000057441) 2020-10-19T19:23:52Z 2020-10-19T19:23:52Z 2020-05 2020-03 2020-10-06T16:59:03Z Article http://purl.org/eprint/type/JournalArticle 1433-7851 1521-3773 https://hdl.handle.net/1721.1/128119 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 en http://dx.doi.org/10.1002/anie.202003478 Angewandte Chemie - International Edition Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Prof. Pentelute via Ye Li |
| spellingShingle | Pomplun, Sebastian Johannes Shugrue, Christopher R. Schmitt, Adeline M. Schissel, Carly K. Farquhar, Charlotte E. Pentelute, Bradley L. Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title | Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title_full | Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title_fullStr | Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title_full_unstemmed | Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title_short | Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release |
| title_sort | secondary amino alcohols traceless cleavable linkers for use in affinity capture and release |
| url | https://hdl.handle.net/1721.1/128119 |
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