New Fluorous Photoaffinity Labels (F-PAL) and Their Application in V-ATPase Inhibition Studies
Autor(en): | Burkard, Nadja Bender, Tobias Westmeier, Johannes Nordmann, Christin Huss, Markus Wieczorek, Helmut Grond, Stephanie von Zezschwitz, Paultheo |
Stichwörter: | ACID; Bafilomycin; BAFILOMYCIN/CONCANAMYCIN-BINDING-SITE; Chemistry; Chemistry, Organic; Concanamycin; CONCANAMYCIN-A; Fluorous chromatography; P-TYPE; Perfluorinated reagents; Photoaffinity labeling; SUBUNIT-C; V-ATPase inhibitors; VACUOLAR ATPASE | Erscheinungsdatum: | 2010 | Herausgeber: | WILEY-V C H VERLAG GMBH | Journal: | EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | Volumen: | 2010 | Ausgabe: | 11 | Startseite: | 2176 | Seitenende: | 2181 | Zusammenfassung: | (Trifluoromethyl)diazirines are well established photoaffinity labels (PAL) used in biochemical investigations to create covalent ligand-receptor bonds. Two new diazirinylbenzoic acids 8b,c with perfluorobutyl and perfluorooctyl chains (F-PAL) were efficiently prepared from p-bromobenzaldehyde and attached to the highly potent and specific V-ATPase inhibitors 21-deoxyconcanolide A (2) and bafilomycin A(1) (5), deriving from the natural product pool from Streptomyces producer strains. The labelled derivatives 17 and 18 were efficiently purified by fluorous solid-phase extraction. Functional biochemical assays with the V-ATPase holoenzymes proofed strong inhibition activities. So far, radioactive isotopes or biotin-tags have mainly been used for tracing compounds in photoaffinity studies. The C4F9- and C8F17-fluorous tags aim to enable advantageous separation and identification of labelled peptide fragments by fluorous chromatography followed by MS analysis. Therefore, F-PAL represents an innovative new concept for binding site determination and should significantly accelerate and simplify such biochemical investigations. |
ISSN: | 1434193X | DOI: | 10.1002/ejoc.200901463 |
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geprüft am 19.05.2024