![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB |
Preview |
PDF (Spplementary Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
5MB |
| Item Type: | Article |
|---|---|
| Title: | Vinylphosphonites for staudinger-induced chemoselective peptide cyclization and functionalization |
| Creators Name: | Kasper, M.A, Glanz, M., Oder, A., Schmieder, P., von Kries, J.P. and Hackenberger, C.P.R. |
| Abstract: | In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity for a following thiol addition. We show that by varying the phosphonamidate ester substituent we can fine-tune the reactivity of the thiol addition and even control the functional properties of the final conjugate. Furthermore, we observed a drastic increase in thiol addition efficiency when the SPhR is carried out in the presence of a thiol substrate in a one-pot reaction. Hence, we utilize vinylphosphonites for the chemoselective intramolecular cyclization of peptides carrying an azide-containing amino acid and a cysteine in high yields. Our concept was demonstrated for the stapling of a cell-permeable peptidic inhibitor for protein–protein interaction (PPI) between BCL9 and beta-catenin, which is known to create a transcription factor complex playing a role in embryonic development and cancer origin, and for macrocyclization of cell-penetrating peptides (CPPs) to enhance the cellular uptake of proteins. |
| Keywords: | Protein Modification, Drug, Strategies, Stability, Chemistry |
| Source: | Chemical Science |
| ISSN: | 2041-6520 |
| Publisher: | Royal Society of Chemistry |
| Volume: | 10 |
| Number: | 25 |
| Page Range: | 6322-6329 |
| Date: | 7 July 2019 |
| Official Publication: | https://doi.org/10.1039/C9SC01345H |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
