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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