Chemoselective thiofunctionalization and 35S radiolabeling of peptides/proteins – Thio-Fun

We propose here to develop a novel approach based on palladium catalysis for specific thioconjugation of peptides or proteins with various thiols (including 35S labeling), under conditions compatible with the most sensitive proteins. The originality of this strategy is based on Page 3 of 14
the «tag-and-modify« approach, which involves the sequential installation of p-iodophenylalanine (pIPhe) on the protein as a reactive chemical tag (the electrophilic «tag«, completely unreactive in the absence of catalyst) and its selective modification with various thiols.

Important preliminary results were obtained on the mercapolization of halogenated aryls. The reaction takes place under mild conditions at Ta. The extension to peptides is in progress

A study study we have developed a simple and efficient reaction to access the amino acid Trt-thioTyr (NHFmoc) in order to engage it as a «building block« in SPPS for the synthesis of peptides having a thio-Tyr .

Finally, we were interested in a new method for functionalizing peptides. The approach consists this time in using a bidirectional (bifunctional) system on which we could consider two orthogonal transformations.

The preliminary results presented encourage us to continue to develop the ongoing projects.

The current projects not being finished, we considered it necessary to complete the studies before publishing