Kroll, Carsten. Oligoprolin als molekulares Gerüst für multivalente, peptidische Tumor-Targeting Liganden. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10668
In our approach azido-functionalized oligoprolines are used as helical, conformationally well-defined scaffolds to display peptidic targeting vectors. As targeting vectors, bombesin agonists and antagonists with a high affinity towards gastrin releasing peptide receptors (GRP-R) are employed. Conjugation to the scaffold has been achieved via copper catalyzed "click chemistry". The modular synthesis of the molecules is performed on solid support. Additionally, a DOTA-chelator was introduced for labelling with different radiometals. --
A series of molecules, differing in type and composition of the targeting vectors has been synthesized. In vitro studies with 177Lu labelled ligands show excellent binding and high internalization of the novel hybride ligands. The experiments show, that the uptake depends on the distance between the two binding elements and that there is an optimal distance of 20 Å between the two recognition elements. PET images of mice with 68Ga labelled ligands demonstrate the high and specific uptake in the tumor. Biodistribution experiments showed that tumor uptake of the best hybrid ligand is much higher compared to established monovalent controls, and washout is slower. A hypothesis is presented which might explain the high uptake of the best hybride ligand.
|Committee Members:||Seebeck, Florian|
|Faculties and Departments:||05 Faculty of Science > Departement Chemie > Former Organization Units Chemistry > Bioorganische Chemie (Wennemers)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||171 S.|
|Last Modified:||30 Jun 2016 10:55|
|Deposited On:||13 Mar 2014 14:09|
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