期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 14, 期 31, 页码 9516-9529出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.200801046
关键词
antibody mimics; epitome imprinting; molecular recognition; phosphopeptides; proteomics
资金
- European Community [HMN-CT-2002-00189]
Hyperphosphorylation at tyrosine is commonly observed in tumor preoteomes and hence, specific phosphoproteins or phosphopeptides could serve as markers useful for cancer diagnostics and therapeutics. The analysis of such targets is, however, a challenging task, because of their commonly low abundance and the lack of robust and effective preconcentration techniques. As a robust alternative to the commonly used immunoaffinity techniques that rely on phosphotyrosine-(pTyr)-specific antibodies, we have developed an epitope-imprinting strategy that leads to a synthetic pTyr-selective imprinted polymer receptor. The binding site incorporates two monourea ligands placed by preorganization around a pTyr dianion template. The tight binding site displayed good binding affinities for pTyr template, in the range of that observed for corresponding antibodies, and a clear preference of pTyr over phosphoserine (pSer). In further analogy to the antibodies, the imprinted polymer was capable of capturing short tyrosine phosphorylated peptides in the presence of an excess of their non-physphyrylated counterparts or peptides phosphorylated at serine.
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