Late-stage functionalisation of peptides on the solid phase by an iodination-substitution approach
The functionalisation of peptides at a late synthesis stage holds great potential, for example, for the synthesis of peptide pharmaceuticals, fluorescent biosensors or peptidomimetics. Here we describe an on-resin iodination-substitution reaction sequence on homoserine that is also suitable for pept...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
September 6, 2022
|
| In: |
Chemistry - a European journal
Year: 2022, Volume: 28, Issue: 50, Pages: 1-7 |
| ISSN: | 1521-3765 |
| DOI: | 10.1002/chem.202201339 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/chem.202201339 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202201339 
|
| Author Notes: | Marius Werner, Julius Pampel, Truc Lam Pham, and Franziska Thomas |
| Summary: | The functionalisation of peptides at a late synthesis stage holds great potential, for example, for the synthesis of peptide pharmaceuticals, fluorescent biosensors or peptidomimetics. Here we describe an on-resin iodination-substitution reaction sequence on homoserine that is also suitable for peptide modification in a combinatorial format. The reaction sequence is accessible to a wide range of sulfur nucleophiles with various functional groups including boronic acids, hydroxy groups or aromatic amines. In this way, methionine-like thioethers or thioesters and thiosulfonates are accessible. Next to sulfur nucleophiles, selenols, pyridines and carboxylic acids were successfully used as nucleophiles, whereas phenols did not react. The late-stage iodination-substitution approach is not only applicable to short peptides but also to the more complex 34-amino-acid WW domains. We applied this strategy to introduce 7-mercapto-4-methylcoumarin into a switchable ZnII responsive WW domain to design an iFRET-based ZnII sensor. |
|---|---|
| Item Description: | Online veröffentlicht am 14. Juni 2022 Gesehen am 19.12.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1521-3765 |
| DOI: | 10.1002/chem.202201339 |