Late-stage amination of peptides on the solid phase
Late-stage peptide modification is a powerful tool for rapidly generating a library of peptide mimetics, for example, for drug discovery or catalyst development. While late-stage modifications exist for many types of structural features, methods for introducing amines into peptides via a late-stage...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
05 May 2025
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| In: |
Chemistry - a European journal
Year: 2025, Volume: 31, Issue: 34, Pages: 1-8 |
| ISSN: | 1521-3765 |
| DOI: | 10.1002/chem.202501229 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/chem.202501229 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202501229 
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| Author Notes: | Julian Brinkhofer, Marius Werner, Agon Kokollari, Shih-Yu Pan, Christian Klein, Truc Lam Pham, and Franziska Thomas |
| Summary: | Late-stage peptide modification is a powerful tool for rapidly generating a library of peptide mimetics, for example, for drug discovery or catalyst development. While late-stage modifications exist for many types of structural features, methods for introducing amines into peptides via a late-stage approach are rare, despite their enormous potential for the development of peptide therapeutics. Here we present a protocol for introducing amines into peptides by our established on-resin iodination-substitution approach. Our method is compatible with a wide variety of amines, including primary and secondary amines, anilines, and other heteroaromatic N-nucleophiles mostly giving good to excellent yields. We introduce amines that are pharmacologically relevant as well as those that can impart catalytic or metal-binding properties into the peptide of interest. As a proof-of-concept study, we introduce the metal ligand tris(2-aminoethyl)amine (tren) into a tryptophan zipper scaffold using our late-stage amination approach to explore metal-induced stapling. Indeed, metal complexation via the tren ligand resulted in a thermal stabilization of more than 30 K in one of our tryptophan zipper designs. |
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| Item Description: | Gesehen am 09.09.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1521-3765 |
| DOI: | 10.1002/chem.202501229 |