| Zugriffsnummer | 14717 |
| Dokumenttyp | Zeitschriftenartikel |
| Sprache | Englisch |
| Titel | A complete substitutional analysis of VIP for better tumor imaging properties |
| Autor(in); Institution |
Bhargava, Sarah; Institut für Medizinische Immunologie, Unversitätsklinikum Charité, Berlin, GERMANY
Licha, Kai; Institut für Diagnostikforschung GmbH an der FU Berlin, GERMANY
Knaute, Tobias; Institut für Medizinische Immunologie, Universitätsklinikum Charité, Berlin, GERMANY
Ebert, Bernd; 8.12, Biomedizinische Optik und NMR-Messtechnik, PTB-Berlin
Becker, Andreas; Institut für Diagnostikforschung GmbH an der FU Berlin, GERMANY
Hessenius, Carsten; Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Universitätsklinikum Charité, Berlin, GERMANY
Schneider-Mergener, Jens; Institut für Medizinische Immunologie, Universitätsklinikum Charité, Berlin, GERMANY
Volkmer-Engert, Rudolf; Institut für Medizinische Immunologie, Universitätsklinikum Charité, Berlin, GERMANY
|
| Quelle/Jahr | Journal of Molecular Recognition: 15 (2002), 3, 145 - 153 |
| ISSN | 0952-3499 |
| DOI | |
| Verlag | Chichester: Wiley |
| Freie Schlagworte | vasoactive intestinal peptide ; VPAC1 ; substitutional analysis ; spot synthesis ; cyanine dyes ; optical imaging ; tumor diagnosis |
| Zusammenfassung | Since numerous tumor cells over-express the vasoactive intestinal peptide (VIP) receptor subtype 1 (VPAC1), VIP-dye conjugates would be useful as contrast agents for in vivio optical imaging. However, proteolytic degradation of VIP in vivio limits their diagnostic use and highlights the need for structurally optimized VIP derivatives with improved pharmacokinetics. Here, we applied parallel nano-synthesis of cleavable peptides on cellulose membranes to perform a complete VIP substitutional analysis. The resulting 532 VIP-dye analogues were tested for cell binding by flow cytometry and provide a detailed analysis of amino acid positions essential for binding to VPAC1 over-expressing cells. A VIP supermotif derived from the substituting analysis results provides an excellent reference point for further optimization. Substituting Asp8 by arginine resulted in the [Arg8]-VIP dye-conjugate, which not only counteracts the negative effect of the dye, but also shows increased stability towards proteolytic degradation, good tumor-to-tissue contrast in mice and longer half-life in vivio. |
Zitierung
Bhargava, S., Licha, K., Knaute, T., Ebert, B., Becker, A., Hessenius, C., Schneider-Mergener, J., & Volkmer-Engert, R. (2002). A complete substitutional analysis of VIP for better tumor imaging properties. Journal of Molecular Recognition, 15(3), 145–153. https://doi.org/10.1002/jmr.565