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Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release
Author(s) -
Pomplun Sebastian,
Shugrue Christopher R.,
Schmitt Adeline M.,
Schissel Carly K.,
Farquhar Charlotte E.,
Pentelute Bradley L.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202003478
Subject(s) - linker , peptide , reductive amination , chemistry , combinatorial chemistry , amino acid , solid phase synthesis , serine , cleavage (geology) , peptide synthesis , peptide sequence , biochemistry , catalysis , enzyme , biology , computer science , paleontology , operating system , fracture (geology) , gene
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 NaIO 4 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.