dc.contributor.author
Accorsi, Matteo
dc.contributor.author
Tiemann, Markus
dc.contributor.author
Wehrhan, Leon
dc.contributor.author
Finn, Lauren M.
dc.contributor.author
Cruz, Ruben
dc.contributor.author
Rautenberg, Max
dc.contributor.author
Emmerling, Franziska
dc.contributor.author
Heberle, Joachim
dc.contributor.author
Keller, Bettina G.
dc.contributor.author
Rademann, Jörg
dc.date.accessioned
2022-06-13T05:25:33Z
dc.date.available
2022-06-13T05:25:33Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/35066
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-34783
dc.description.abstract
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, including molecular dynamics simulations.
en
dc.format.extent
6 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
Chemical Biology
en
dc.subject
Drug Development
en
dc.subject
Pentafluorophosphates
en
dc.subject
Phosphotyrosine Biomimetics
en
dc.subject
Protein Tyrosine Phosphatases
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften
dc.title
Pentafluorophosphato-Phenylalanines: Amphiphilic Phosphotyrosine Mimetics Displaying Fluorine-Specific Protein Interactions
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e202203579
dcterms.bibliographicCitation.doi
10.1002/anie.202203579
dcterms.bibliographicCitation.journaltitle
Angewandte Chemie International Edition
dcterms.bibliographicCitation.number
25
dcterms.bibliographicCitation.volume
61
dcterms.bibliographicCitation.url
https://doi.org/10.1002/anie.202203579
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation
Physik
refubium.affiliation.other
Institut für Chemie und Biochemie
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refubium.affiliation.other
Institut für Pharmazie
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refubium.funding
DEAL Wiley
refubium.note.author
Die Publikation wurde aus Open Access Publikationsgeldern der Freien Universität Berlin gefördert.
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.eissn
1521-3773
refubium.resourceType.provider
WoS-Alert