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Peptide Arrays for Development of PDGFRβ Affine Molecules

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Abstract

Purpose

Peptide arrays represent an attractive method for identification of amino acid motifs that bind to target structures. Spotting derivatives of the linear peptide platelet-derived growth factor receptor (PDGFR)-P1, which has been identified to bind the extracellular domain of the platelet-derived growth factor receptor beta, allows the synchronous investigation of the target affinity of numerous ligands.

Procedures

A peptide array randomizing PDGFR-P1 was constructed by replacement of each amino acid by all 20 natural amino acids. Incubation of the array with PDGFRβ and fibroblast growth factor receptor as negative control target was performed. Selected derivatives and fragments of PDGFR-P1 were chemically synthesized, radiolabeled, and evaluated in cell-based assays, using human pancreatic carcinoma BxPC3 and human breast cancer MCF7 cells.

Results

Binding capacity was increased for the derivate yG2 by exchange of 7S to 7R. Competition experiments demonstrated a binding decrease with increasing competitor concentration. Serum stability of yG2 was improved compared to the native ligand.

Conclusion

Peptide arrays were successfully applied for the improvement of the PDGFRβ binding peptide PDGFR-P1.

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Acknowledgments

This project has been financed by the Federal Ministry of Education and Research (BMBF) of Germany (Project MOBITECH-BIOTRACE, Nr.: 13N10269). Vasileios Askoxylakis received financial support by the Medical Faculty of the University of Heidelberg.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany

    Annabell Marr, Felix Nissen & Uwe Haberkorn

  2. Clinical Cooperation Unit Molecular Radiooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Peter E Huber & Vasileios Askoxylakis

  3. Intavis Bioanalytical Instruments AG, Heidelberg, Germany

    Daniel Maisch

  4. Clinical Cooperation Unit Nuclear Medicine, DKFZ, Heidelberg, Germany

    Annette Altmann & Uwe Haberkorn

  5. Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany

    Shoaib Rana, Jürgen Debus, Peter E Huber & Vasileios Askoxylakis

Authors
  1. Annabell Marr
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  2. Felix Nissen
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  3. Daniel Maisch
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  4. Annette Altmann
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  5. Shoaib Rana
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  6. Jürgen Debus
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  7. Peter E Huber
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  8. Uwe Haberkorn
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  9. Vasileios Askoxylakis
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Corresponding author

Correspondence to Vasileios Askoxylakis.

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Marr, A., Nissen, F., Maisch, D. et al. Peptide Arrays for Development of PDGFRβ Affine Molecules. Mol Imaging Biol 15, 391–400 (2013). https://doi.org/10.1007/s11307-013-0616-0

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  • DOI: https://doi.org/10.1007/s11307-013-0616-0

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