Title of the PhD project: Targeted complexes of macrocyclic ligands
Contact person and project supervisor: Prof. Petr Hermann, email@example.com
Website of the research group: http://web.natur.cuni.cz/anorchem/koordchem/en
Research group name: Group of Coordination and Bioinorganic Chemistry
Leader of the research group: Prof. Petr Hermann, firstname.lastname@example.org
Department of Inorganic Chemistry
Modern medicine aims at personalized approach (diagnosis/treatment based on “biochemistry” of an individual patient, a thera(g)nostic approach), which is mostly used to treat different cancers. It requires utilization of probes/tracers/conjugates which have to be localized (ideally) only in the diseased tissue. This approach requires a conjugation of a drug to a targeting biovector, which directs the conjugate to diseased tissue on a basis of different biochemical signature of diseased and healthy tissues. Among different drug molecules, targeted metal complexes (which must be stable in vivo) have attracted a lot of attention and, despite that a number of them are clinically used, their research is still a very active field. These complexes are mostly based on macrocyclic ligands and their properties are tuneable by design of each part (the biological vector and complex of the macrocyclic ligand).
The project will be focused on the synthesis of bifunctional macrocyclic ligands, which will be conjugated to biologically active small molecules serving as targeting units. The project will consist of two parts. Ligands endowed with desired properties (an efficient metal ion binding, kinetic inertness of their complexes, suitable hydrophilicity etc.) and with a suitable reactive bifunctional group will be designed and synthesized. The ligands and their complexes will be investigated by techniques appropriate for macrocyclic complexes (spectroscopic techniques, thermodynamics/kinetics). Several targeting small molecules will be chosen (in collaboration with biology labs) and synthesized if necessary. The bifunctional ligands and the small biomolecules will be modified to be mutually synthetically compatible while biological properties of the conjugates will be kept as good as possible. Conjugation techniques will be tested. The metal-labelled conjugates will be investigated with participation of collaborating laboratories for in vitro (cell studies, stability in biological media, affinity to cell receptors etc.) and in vivo (animal studies).
PhD student should be able to work independently and should have a good knowledge of organic synthesis/purification techniques. The student should be also able to characterize (purity, identity, molecular properties) the prepared compounds (mainly metal complexes) by common chromatographic/spectroscopic techniques such as e.g. multinuclear NMR or HPLC. Previous experience with any aspect of biochemical work or molecular imaging is welcome but not required. The student may expect work on a multidisciplinary project, which will involve organic synthesis employing also modern conjugation techniques, study of coordination chemistry of prepared complexes and (in collaboration) investigation of the prepared compounds in biological media, cells or even in vivo (animal studies).
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