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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 146776
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 01.08.2013 - 31.07.2014
Approved amount 67'388.00
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All Disciplines (2)

Discipline
Inorganic Chemistry
Biochemistry

Keywords (7)

Metal Complexes; Metal Bioconjugates; Inorganic Chemical Biology; Caged Compounds; Photo-release; Bioorganometallic Chemistry; Medicinal Inorganic Chemistry

Lay Summary (French)

Lead
Le but de ce projet est de donner de nouveaux outils au domaine de la chimie biologique en permettant un control spatial et temporel de la libération de complexes métalliques dans des cellules vivantes.
Lay summary

Le but de notre groupe de recherche à l'Institut de Chimie Inorganique de l'Université de Zurich est d'utiliser la lumière comme "interrupteur" pour libérer spécifiquement des complexes métalliques d'importance biologique ou médicale dans des cellules vivantes. Ainsi, nous espérons pouvoir donner de nouveaux outils au domaine de la chimie biologique en permettant un control spatial et temporel de la libération de complexes métalliques dans des cellules vivantes.

Pour ce faire, nous préparons des conjugués métalliques qui ont des propriétés biologiques ou médicales. Ces derniers sont rendus inactifs par couplage à des groupes photolabiles. Ainsi sont formées des "cages métalliques". De manière importante, ces cages sont aussi liées à des biomolécules (transporteurs cellulaires spécifiques, signaux localisateurs, etc...) pour permettre une livraison précise des complexes métalliques dans des organelles cellulaires. Par "activation lumineuse", les complexes métalliques sont libérés et peuvent exercer une fonction spécifique dans la cellule comme de la cytotoxicité, inhibition d'enzymes, etc...

 

Direct link to Lay Summary Last update: 25.03.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
A Deadly Organometallic Luminescent Probe: Anticancer Activity of a Re(I) Bisquinoline Complex
Kitanovic I., Can S., Alborzinia H., Kitanovic A., Pierroz V., Leonidova A., Pinto A., Molteni R., Spingler B., Ferrari S., Steffen A., Metzler-Nolte N., Wölfl S., Gasser G. (2014), A Deadly Organometallic Luminescent Probe: Anticancer Activity of a Re(I) Bisquinoline Complex, in Chem. Eur. J., 20, 2496-2507.
Enhanced Cytotoxicity through Conjugation of a “Clickable” Luminescent Re(I) Complex to a Cell-Penetrating Lipopeptide
Leonidova A., Pierroz V., Adams L., Borlow N., Ferrari S., Graham B., Gasser G. (2014), Enhanced Cytotoxicity through Conjugation of a “Clickable” Luminescent Re(I) Complex to a Cell-Penetrating Lipopeptide, in ACS Med. Chem. Lett., 5, 809-814.
Photo-Induced Uncaging of a Specific Re(I) Organometallic Complex in Living Cells
Leonidova A., Pierroz V., Rubbiani R., Lan Y., Schmitz A.G., Kaech A., Sigel R.K.O., Ferrari S., Gasser G. (2014), Photo-Induced Uncaging of a Specific Re(I) Organometallic Complex in Living Cells, in Chem. Sci., 5, 4044-4056.
Towards Cancer Cell-Specific Phototoxic Organometallic Rhenium(I) Complexes
Leonidova A., Pierroz V., Rubbiani R., Heier J., Ferrari S., Gasser G. (2014), Towards Cancer Cell-Specific Phototoxic Organometallic Rhenium(I) Complexes, in Dalton Trans., 43, 4287-4294.
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.
In Vivo Antischistosomal Activity Studies and In Vitro Metabolic Profile of (
Patra M., Ingram K., Leonidova A., Pierroz V., Ferrari S., Robertson M., Todd M.H., Keiser J., Gasser G. (2013), In Vivo Antischistosomal Activity Studies and In Vitro Metabolic Profile of (, in J. Med. Chem., 56, 9192-9198.

Associated projects

Number Title Start Funding scheme
129910 Photo-Induced Uncaging of Metal Complexes in Living Cells 01.08.2010 Project funding (Div. I-III)
133568 Caged Metal Complexes as Tools in Inorganic Chemical Biology 01.03.2011 SNSF Professorships
157545 Caged Metal Complexes as Tools in Inorganic Chemical Biology 01.03.2015 SNSF Professorships

Abstract

The main focus of our research group at the Institute of Inorganic Chemistry of the University of Zurich is currently to use light as an external trigger to specifically release metal complexes of biological and medicinal relevance in living cells. We aim to give new tools in the field of chemical biology by enabling a spatial and temporal release of metal compounds in living cells. For this purpose, we are preparing metal-containing bioconjugates which hold biologically or medicinally relevant metal complexes. The latter have been rendered inactive by a chemical coupling to a photolabile protecting group (PLPG) to form so-called metal-caged compounds. Importantly, our metal-caged compounds are also linked to a biomolecule (e.g. specific cellular transporter, localisation signal, etc...) in order to enable an accurate delivery of the metal complexes to distinct cells or cellular organelles. Upon light activation, the metal complexes are then liberated and undertake a specific function within the cell such as cytotoxicity, enzyme inhibition, etc…Anna Leonidova, who was the first PhD student in our group, pioneered this research and obtained very promising preliminary results during the first two years of her PhD thesis. She successfully achieved, to the best of our knowledge, the first release of two specific metal complexes, namely aminoferrocene and a Re tricarbonyl derivative, in living cells. She is currently assessing the biological and medicinal potentials of the release. In this proposal, we present the research to be undertaken by Anna Leonidova to finish up this project and hence complete her dissertation. We are expecting that several publications could be published if a one-year extension to this SNSF project was granted.
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