Riechers, Alexander and Grauer, Andreas and Ritter, Stefan and Sperl, Bianca and Berg, Thorsten and Koenig, Burkhard (2010) Binding of phosphorylated peptides and inhibition of their interaction with disease-relevant human proteins by synthetic metal-chelate receptors. JOURNAL OF MOLECULAR RECOGNITION, 23 (3). pp. 329-334. ISSN 0952-3499,
Full text not available from this repository. (Request a copy)Abstract
The modulation of biological signal transduction pathways by masking phosphorylated amino acid residues represents a viable route toward pharmacologic protein regulation. Binding of phosphorylated amino acid residues has been achieved with synthetic metal-chelate receptors. The affinity and selectivity of such receptors can be enhanced if combined with a second binding site. We demonstrate this principle with a series of synthetic ditopic metal-chelate receptors, which were synthesized and investigated for their binding affinity to phosphorylated short peptides under conditions of physiological pH. The compounds showing highest affinity were subsequently used to inhibit the interaction of the human STAT1 protein to a peptide derived from the interferon-gamma receptor, and between the checkpoint kinase Chk2 and its preferred binding motif. Two of the investigated ditopic synthetic receptors show a significant increase in inhibition activity. The results show that regulation of protein function by binding to phosphorylated amino acids is possible. The introduction of additional binding sites into the synthetic receptors increases their affinity, but the flexibility of the structures investigated so far prohibited stringent amino acid sequence selectivity in peptide binding. Copyright (C) 2009 John Wiley & Sons, Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARBONIC-ANHYDRASE-I; GROWTH-FACTOR; SIGNALING PATHWAYS; MASS-SPECTROMETRY; CANCER-THERAPY; KINASE; IDENTIFICATION; TRANSCRIPTION; ACTIVATION; MOLECULE; metal-chelates; emission spectroscopy; protein binding; phosphate binding; protein-protein interaction; molecular recognition |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Aug 2020 05:01 |
| Last Modified: | 03 Aug 2020 05:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24782 |
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