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Photo-Induced Uncaging of Metal Complexes in Living Cells

English title Photo-Induced Uncaging of Metal Complexes in Living Cells
Applicant Gasser Gilles
Number 129910
Funding scheme Project funding (Div. I-III)
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Inorganic Chemistry
Start/End 01.08.2010 - 31.07.2013
Approved amount 198'574.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Biochemistry

Keywords (8)

Inorganic Chemical Biology; Bioorganometallic Chemistry; Medicinal Inorganic Chemistry; Metal Complexes; Peptide Nucleic Acid (PNA); Caged Compounds; Metal Bioconjugates; Photo-release

Lay Summary (English)

Lead
Lay summary
Chemical Biology is the extraordinary endeavour of understanding, identifying and/or influencing biological processes in living cells using small molecules. Some metal-based compounds have been (and continue to be) selected to assist in this quest, for example, as anti-cancer agents, artificial proteases, artificial nucleases, artificial transporters of Ca2+, probes to demonstrate DNA charge transport, delivery vehicles for CO and NO, imaging agents, etc. All these biological applications employing metal complexes/organometallics have recently been referred to as Inorganic Chemical Biology.An important and useful strategy applied in Chemical Biology for the study of living organisms is the use of light-responsive caged compounds. In these studies, biologically relevant molecules (glutamates, proteins, nucleic acids, etc…), rendered inactive by a photolabile protecting group (PLPG), were introduced into living cells/organisms. Upon activation of light, the irreversible release of these biologically active molecules at a specific time and location could be achieved. Despite great success observed in these such studies, the examples of released metal complexes for biological purposes are currently non-existent.With this in mind, in this proposal, I present a general concept to specifically release metal complexes of biological/medicinal relevance from metal-containing bioconjugates using light as an external trigger. Biologically specific cellular transporters/recognition units will be coupled, using different synthetic methods to photoremovable protecting groups, to which metal complexes with different properties will be attached. Upon light activation, the metal complexes will be liberated and will therefore be able to undertake a specific function within the cell.The general outcome from this cross-disciplinary research will be of significant interest in various areas such as inorganic chemistry, bioorganometallic chemistry, medicinal chemistry, biochemistry and biophysical chemistry.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
An Environmentally Benign and Cost-Effective Synthesis of Aminoferrocene and Aminoruthenocene
Leonidova A., Joshi T., Nipkow D., Frei A., Penner J.-E., Konatschnig S., Patra M, Gasser G. (2013), An Environmentally Benign and Cost-Effective Synthesis of Aminoferrocene and Aminoruthenocene, in Organometallics, 32, 2037-2040.
Molecular and Cellular Characterization of the Biological Effects of Ruthenium(II) Complexes Incorporating 2-Pyridyl-2-Pyrimidine-4-Carboxylic Acid
Pierroz V., Joshi T., Leonidova A., Mari C., Schur J., Ott I., Spiccia L., Ferrari S., Gasser G. (2012), Molecular and Cellular Characterization of the Biological Effects of Ruthenium(II) Complexes Incorporating 2-Pyridyl-2-Pyrimidine-4-Carboxylic Acid, in J. Am. Chem. Soc., 134, 20376-20387.
Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2'-dipicolylamine.
Gasser Gilles, Jäger Katrin, Zenker Martin, Bergmann Ralf, Steinbach Jörg, Stephan Holger, Metzler-Nolte Nils (2010), Preparation, 99mTc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2'-dipicolylamine., in Journal of inorganic biochemistry, 104(11), 1133-40.
Towards Cancer Cell-Specific Phototoxic Organometallic Rhenium(I) Complexes
Leonidova A., Pierroz V., Rubbiani R., Heier J., Ferrari S., Gasser G., Towards Cancer Cell-Specific Phototoxic Organometallic Rhenium(I) Complexes, in Dalton Trans..

Awards

Title Year
SCNAT/SCS Chemistry Travel Award 2013

Associated projects

Number Title Start Funding scheme
146776 Photo-Induced Uncaging of Metal Complexes in Living Cells 01.08.2013 Project funding (Div. I-III)
133568 Caged Metal Complexes as Tools in Inorganic Chemical Biology 01.03.2011 SNSF Professorships
144964 Upgrade of the UZH NMR Core Facility 01.12.2012 R'EQUIP
126404 Synthesis of PNA-Metal Bioconjugates by "Copper-Free" and "Photo" Click Chemistry: An Approach towards the in Vitro Attachment of Organometallics to Biomolecules 01.03.2010 Ambizione

Abstract

In this proposal, I present a general concept to specifically release metal complexes of biological/medicinal relevance from metal-containing bioconjugates using light as an external trigger. Biologically specific cellular transporters/recognition units (peptides, proteins, nucleic acids, peptide nucleic acids (PNAs), biotin, (poly)saccharides, hormones, lipids, etc…) will be coupled, using different synthetic methods (native chemical ligation, peptide coupling, click chemistry, etc...), to photoremovable protecting groups, to which metal complexes with different properties will be attached. Upon light activation, the metal complexes will be liberated and will therefore be able to undertake a specific function within the cell (cytotoxicity, imaging, enzyme inhibition, DNA/RNA/protein cleavage, etc…).
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