Premium
A Selenium‐Based Click AdoMet Analogue for Versatile Substrate Labeling with Wild‐Type Protein Methyltransferases
Author(s) -
Willnow Sophie,
Martin Michael,
Lüscher Bernhard,
Weinhold Elmar
Publication year - 2012
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201100781
Subject(s) - click chemistry , methyltransferase , chemistry , methylation , bioorthogonal chemistry , protein methylation , methionine , cycloaddition , azide , triazole , glutamine , biochemistry , stereochemistry , combinatorial chemistry , amino acid , catalysis , dna , organic chemistry
Protein methylation is catalyzed by S ‐adenosyl‐ L ‐methionine‐dependent protein methyltransferases (MTases), and this posttranslational modification serves diverse cellular functions. Some MTases seem to exhibit broad substrate specificities and comprehensive methods for target profiling are needed. Here we report the synthesis of a new AdoMet analogue for enzymatic transfer of a small propargyl group and labeling of modified proteins through copper‐catalyzed azide–alkyne cycloaddition (CuAAC). Replacement of sulfur by selenium strongly enhanced the stability of the progargylic cofactor, leading, in combination with better activation by the selenonium center, to higher enzymatic reactivity. A broad spectrum of wild‐type protein MTases acting on lysine, arginine, and glutamine residues accept this cofactor and modified substrates can be efficiently labeled by CuAAC click chemistry.