Late-Stage Functionalisation of Peptides on the Solid Phase by an Iodination-Substitution Approach |
| |
Authors: | Marius Werner Julius Pampel Truc Lam Pham Prof. Dr. Franziska Thomas |
| |
Affiliation: | 1. Institute of Organic Chemistry, Heidelberg University, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany;2. Department of Chemical Biology, Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany |
| |
Abstract: | 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. |
| |
Keywords: | solid-phase synthesis peptides late-stage functionalisation WW domains biosensors |
|
|