A Phosphotyrosine‐Imprinted Polymer Receptor for the Recognition of Tyrosine Phosphorylated Peptides

Hyperphosphorylation at tyrosine is commonly observed in tumor proteomes 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 abundanc...

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Veröffentlicht in:Chemistry : a European journal Jg. 14; H. 31; S. 9516 - 9529
Hauptverfasser: Emgenbroich, Marco, Borrelli, Cristiana, Shinde, Sudhirkumar, Lazraq, Issam, Vilela, Filipe, Hall, Andrew J., Oxelbark, Joakim, De Lorenzi, Ersilia, Courtois, Julien, Simanova, Anna, Verhage, Jeroen, Irgum, Knut, Karim, Kal, Sellergren, Börje
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Weinheim WILEY‐VCH Verlag 01.01.2008
Wiley
Schlagworte:
antibody mimics
Chemistry
Chemistry, Multidisciplinary
epitome imprinting
Models, Molecular
Molecular Imprinting
molecular recognition
Molecular Structure
Peptides - chemistry
phosphopeptides
Phosphotyrosine - chemistry
Physical Sciences
Polymers - chemistry
proteomics
Science & Technology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Urea - chemistry
PHASE
proteomics
THIOUREA
epitome imprinting
MONOLITHS
antibody mimics
molecular recognition
phosphopeptides
ISSN:0947-6539, 1521-3765, 1521-3765
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Zusammenfassung:Hyperphosphorylation at tyrosine is commonly observed in tumor proteomes 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 the pTyr template, in the range of that observed for corresponding antibodies, and a clear preference for 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‐phosphorylated counterparts or peptides phosphorylated at serine. A useful marker: An epitope‐imprinting strategy leads to a synthetic phosphotyrosine‐selective imprinted polymer receptor. Urea‐mediated imprinting of N,O‐protected phosphotyrosine (see picture) leads to a synthetic receptor capable of selectively extracting phosphotyrosine peptides in the presence of phosphoserine, phosphothreonine, and non‐phosphorylated peptides.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.200801046