Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release. (8th May 2020)

• Record Type: Journal Article
• Authors: Pomplun, Sebastian; Shugrue, Christopher R.; Schmitt, Adeline M.; Schissel, Carly K.; Farquhar, Charlotte E.; Pentelute, Bradley L.
• Is Part Of: Angewandte Chemie. Volume 132:Number 28(2020)
• Page Start: 11663
• Page End: 11669
• Publication Date: 2020-05-08
• Subjects: bioorthogonal chemistry -- cleavable linkers -- oxidative cleavage -- peptide libraries -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202003478
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : Catch and Release : A new cleavable linker based on secondary amino alcohols is reported for application in peptide discovery. The linker is easily incorporated into peptides during on‐resin synthesis and is shown to be rapidly cleaved in the presence of NaIO4 . Peptide‐library and cell‐based experiments demonstrate that this linker enables the recovery of hit sequences after affinity capture.