Zitieren Sie bitte immer diesen URN: urn:nbn:de:kobv:b43-549984
Pentafluorophosphato-Phenylalanines: Amphiphilic Phosphotyrosine Mimetics Displaying Fluorine-Specific Protein Interactions
- Phosphotyrosine residues are essential functional switches in health and disease. Thus, phosphotyrosine biomimetics are crucial for the development of chemical tools and drug molecules. We report here the discovery and investigation of pentafluorophosphato amino acids as novel phosphotyrosine biomimetics. A mild acidic pentafluorination protocol was developed and two PF5-amino acids were prepared and employed in peptide synthesis. Their structures, reactivities, and fluorine-specific interactions were studied by NMR and IR spectroscopy, X-ray diffraction, and in bioactivity assays. The mono-anionic PF5 motif displayed an amphiphilic character binding to hydrophobic surfaces, to water molecules, and to protein-binding sites, exploiting charge and H−F-bonding interactions. The novel motifs bind 25- to 30-fold stronger to the phosphotyrosine binding site of the protein tyrosine phosphatase PTP1B than the best current biomimetics, as rationalized by computational methods, includingPhosphotyrosine residues are essential functional switches in health and disease. Thus, phosphotyrosine biomimetics are crucial for the development of chemical tools and drug molecules. We report here the discovery and investigation of pentafluorophosphato amino acids as novel phosphotyrosine biomimetics. A mild acidic pentafluorination protocol was developed and two PF5-amino acids were prepared and employed in peptide synthesis. Their structures, reactivities, and fluorine-specific interactions were studied by NMR and IR spectroscopy, X-ray diffraction, and in bioactivity assays. The mono-anionic PF5 motif displayed an amphiphilic character binding to hydrophobic surfaces, to water molecules, and to protein-binding sites, exploiting charge and H−F-bonding interactions. The novel motifs bind 25- to 30-fold stronger to the phosphotyrosine binding site of the protein tyrosine phosphatase PTP1B than the best current biomimetics, as rationalized by computational methods, including molecular dynamics simulations.…
Autor*innen: | M. Accorsi, M. Tiemann, L. Wehrhan, Lauren M. Finn, R. Cruz, Max RautenbergORCiD, Franziska EmmerlingORCiD, J. Heberle, B. G. KellerORCiD, J. RademannORCiD |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | Angewandte Chemie International Edition |
Jahr der Erstveröffentlichung: | 2022 |
Organisationseinheit der BAM: | 6 Materialchemie |
6 Materialchemie / 6.0 Abteilungsleitung und andere | |
6 Materialchemie / 6.3 Strukturanalytik | |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlag: | Wiley-VCH GmbH |
Jahrgang/Band: | 134 |
Ausgabe/Heft: | 25 |
Aufsatznummer: | e202203579 |
Erste Seite: | 1 |
Letzte Seite: | 6 |
DDC-Klassifikation: | Naturwissenschaften und Mathematik / Chemie / Analytische Chemie |
Freie Schlagwörter: | Chemical Biology; Drug Development; Pentafluorophosphates; Phosphotyrosine Biomimetics; Protein Tyrosine Phosphatases |
Themenfelder/Aktivitätsfelder der BAM: | Chemie und Prozesstechnik |
DOI: | 10.1002/anie.202203579 |
URN: | urn:nbn:de:kobv:b43-549984 |
ISSN: | 1433-7851 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International |
Datum der Freischaltung: | 13.06.2022 |
Referierte Publikation: | Ja |
Datum der Eintragung als referierte Publikation: | 13.06.2022 |
Schriftenreihen ohne Nummerierung: | Wissenschaftliche Artikel der BAM |