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New Fluorous Photoaffinity Labels (F‐PAL) and Their Application in V‐ATPase Inhibition Studies
Author(s) -
Burkard Nadja,
Bender Tobias,
Westmeier Johannes,
Nardmann Christin,
Huss Markus,
Wieczorek Helmut,
Grond Stephanie,
von Zezschwitz Paultheo
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200901463
Subject(s) - chemistry , photoaffinity labeling , atpase , bafilomycin , covalent bond , enzyme , stereochemistry , combinatorial chemistry , peptide , binding site , chromatography , biochemistry , organic chemistry , apoptosis , autophagy
(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 C 4 F 9 ‐ and C 8 F 17 ‐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.