Medicinal Inorganic Chemistry; Enzyme Inhibitors; Inorganic Chemical Biology; Metal Complexes; Bioorganometallic Chemistry; Photo-release; Caged Compounds
Mari C., Rubbiani R., Gasser G. (2017), Biological Evaluation of Ru(II) Polypyridyl Complexes as Photosensitizers in Photodynamic Therapy, in Inorg. Chim. Acta
, 454C, 21-26.
Vugts Danielle J., Klaver Chris, Sewing Claudia, Poot Alex J., Adamzek Kevin, Huegli Seraina, Mari Cristina, Visser Gerard W. M., Valverde Ibai E., Gasser Gilles, Mindt Thomas L., van Dongen Guus A. M. S. (2017), Comparison of the octadentate bifunctional chelator DFO*-pPhe-NCS and the clinically used hexadentate bifunctional chelator DFO-pPhe-NCS for 89Zr-immuno-PET, in Eur. J. Nucl. Med. Mol. Imag.
, 44, 286-295.
Appold M., Mari C., Lederle C., Elbert J., Schmidt C., Ott I., Stühn B., Gasser G., Gallei M. (2017), Multi-Stimuli Responsive Block Copolymers as Smart Release Platform for a Polypyridyl Ruthenium Complexes, in Polym. Chem.
, 8, 890-900.
Kumari Namita, Huang Huaiyi, Chao Hui, Gasser Gilles, Zelder Felix (2016), A Disassembly Strategy for Imaging Endogenous Pyrophosphate in Mitochondria by Using an FeIII–salen Complex, in ChemBioChem
, 17, 1211-1215.
Hess Jeannine, Patra Malay, Jabbar Abdul, Pierroz Vanessa, Konatschnig Sandro, Spingler Bernhard, Ferrari Stefano, Gasser Robin B., Gasser Gilles (2016), Assessment of the nematocidal activity of metallocenyl analogues of monepantel, in Dalton Trans.
, 45, 17662-17671.
Clède S., Cowan N., Lambert F., Bertrand H.C., Rubbiani R., Patra M., Hess J., Sandt C., Trcera N., Gasser G., Keiser J., Policar C. (2016), Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni, in ChemBioChem
, 17, 1004-1007.
O’Malley W.I., Rubbiani R., Aulsebrook M.L., Grace M.R., Spiccia L., Tuck K.L., Gasser G., Graham B. (2016), Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex “Clicked” to a Lipidated Tat Peptide, in Molecules
, 21, 194-194.
Pierroz V., Rubbiani R., Gentili C., Patra M., Mari C., Gasser G., Ferrari S. (2016), Dual Mode of Cell Death upon the Photo-Irradiation of a RuII polypyridyl Complex in Interphase and Mitosis, in Chem. Sci.
, 7, 6115-6124.
Mari C., Mosberger S., Llorente N., Spreckelmeyer S., Gasser G. (2016), Insertion of Organometallic Moieties into Peptides and Peptide Nucleic Acids using Alternative “Click” Strategies, in Inorg. Chem. Frontiers
, 3, 397-405.
O’Malley W.I., Abdelkader E.H., Aulsebrook M.L., Rubbiani R., Loh C.-T., Grace M.R., Spiccia L., Gasser G., Otting G., Tuck K.L., Graham B. (2016), Luminescent Alkyne-Bearing Terbium(III) Complexes and their Application to Bioorthogonal Protein and Peptide Labeling, in Inorg. Chem.
, 55, 1674-1682.
Patra Malay, Zarschler Kristof, Pietzsch Hans-Jurgen, Stephan Holger, Gasser Gilles (2016), New insights into the pretargeting approach to image and treat tumours, in Chem. Soc. Rev.
, 45, 6415-6431.
Chekkat N., Dahm G., Chardon E., Sitz J., Decossas M., Lambert O., Frisch B., Rubbiani R., Gasser G., Guichard G., Fournel S., Bellemin-Laponnaz S. (2016), N-Heterocyclic Carbene-Polyethyleneimine (PEI) Platinum Complexes show in vitro and in vivo Antitumor Efficacy, in Bioconjugate Chem.
, 27, 1942-1948.
Hess Jeannine, Patra Malay, Rangasamy Loganathan, Konatschnig Sandro, Blacque Olivier, Jabbar Abdul, Mac Patrick, Jorgensen Erik M., Gasser Robin B., Gasser Gilles (2016), Organometallic Derivatization of the Nematocidal Drug Monepantel Leads to Promising Antiparasitic Drug Candidates, in Chem. Eur. J.
, 22, 16602-16612.
Imstepf S., Pierroz V., Rubbiani R., Felber M., Fox T., Gasser G., Alberto R. (2016), Organometallic Rhenium Complexes Divert Doxorubicin to the Mitochondria, in Angew. Chem. Int. Ed.
, 55, 2792-2795.
Mion G., Mari C., Da Ros T., Rubbiani R., Gasser G., Gianferrara T. (2016), Synthesis of New Tumor Targeting Photosensitizers for Photodynamic Therapy and Imagining Applications, in ChemistrySelect
, 2, 190-200.
Hess J., Patra M., Pierroz V., Spingler B., Jabbar A., Ferrari S., Gasser R.B., Gasser G. (2016), Synthesis, Characterization and Biological Activity of Ferrocenyl Analogues of the Anthelmintic Drug Monepantel, in Organometallics
, 35, 3369-3377.
Nikoli, Rangasamy, Gligorijević, Aranđelović S., Radulović, Gasser, Grgurić-Šipka (2016), Synthesis, Characterization and Biological Evaluation of novel Ru(II) Arene Complexes containing intercalating Ligands, in J. Inorg. Biochem.
, 160, 156-165.
Imstepf S., Pierroz V., Raposinho P., Felber M., Fox T., Fernandes C., Gasser G., Santos I. R., Alberto R. (2016), Towards 99mTc-based imaging agents with effective doxorubicin mimetics: a molecular and cellular study, in Dalton Trans.
, 45, 13025-13033.
Anstaett P., Leonidova A., Gasser G. (2015), Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for UV-A induced Photouncaging, in ChemPhysChem
Mari C., Pierroz V., Ferrari S., Gasser G. (2015), Combination of Ru(II) Complexes and Light: New Frontiers in Cancer Therapy, in Chem. Sci.
Li G., Chen Y., Wang J., Wu J., Gasser G., Ji L., Chao H. (2015), Direct Imaging of Biological Sulfur Dioxide Derivatives in Vivo Using a Two-Photon Phosphorescent Probe, in Biomaterials
Huang H., Yu B., Zhang P., Huang J., Chen Y., Gasser G., Ji L., Chao H. (2015), Highly Charged Ruthenium(II) Polypyridyl Complexes as Lysosome-Localized Photosensitizers for Two-Photon Photodynamic Therapy, in Angew. Chem. Int. Ed.
Leonidova A., Foerster C., Zarschler K., Schubert M., Pietzsch H.-J., Steinbach J., Bergmann R., Metzler-Nolte N., Stephan H., Gasser G. (2015), In vivo Demonstration of a Tumor Pretargeting Approach with Peptide Nucleic Acids as Complementary System, in Chem. Sci.
Leonidova A., Anstaett P., Pierroz V., Spingler B., Ferrari S., Gasser G. (2015), Induction of Cytotoxicity through Photo-release of Aminoferrocene, in Inorg. Chem.
Schmitz A.G., Zelger-Paulus S., Gasser G., Sigel R.K.O. (2015), Internal Labeling Strategy of Large RNAs with Minimal Perturbation Using Fluorescent PNA, in ChemBioChem
Mari C., Gasser G. (2015), Lightening up Ruthenium Complexes to Fight Cancer?, in Chimia
Gasser G. (2015), Metal Complexes and Medicine: A Successful Combination, in Chimia
Imstepf Sebastian, Pierroz Vanessa, Raposinho Paula, Bauwens Matthias, Felber Michael, Fox Thomas, Shapiro Adam B., Freudenberg Robert, Fernandes Célia, Gama Sofia, Gasser Gilles, Motthagy Felix, Santos Isabel R., Alberto Roger (2015), Nuclear Targeting with an Auger Electron Emitter Potentiates the Action of a Widely Used Antineoplastic Drug, in Bioconjugate Chem.
Mion G., Gianferrara T., Bergamo A., Gasser G., Pierroz V., Rubbiani R., Vilar R., Leczkowska A., Alessio E. (2015), Phototoxic Activity and DNA Interactions of New Water Soluble Porphyrins and their Re(I) Conjugates, in ChemMedChem
Anstaett P., Leonidova A., Janett E., Bochet C., Gasser G. (2015), Reply to the Commentary by Trentham et al. on “Caged Phosphate and the Slips and Misses in Determination of Quantum Yields for Ultraviolet-A-Induced Photouncaging” by Gasser and Co-Workers, in ChemPhysChem
Mari C., Pierroz V., Leonidova A., Ferrari S., Gasser G. (2015), Towards Selective Light Activated Ru(II)-based Prodrug Candidates, in Eur. J. Inorg. Chem.
Anstaett P., Pierroz V., Ferrari S., Gasser G. (2015), Two-Photon Uncageable Enzyme Inhibitors bearing Targeting Vectors, in Photochem. Photobiol. Sci.
An important and useful strategy applied in Chemical Biology for the study of living cells/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), are introduced into living cells/organisms. Upon light activation, the irreversible release of these biologically active molecules at a specific time and location can be achieved. Despite great success observed in the studies engaging organic compounds, the examples of the selective release of inert metal complexes were, to the best of my knowledge, inexistent at the time of my SNSF application in 2011. My group has recently been the first to demonstrate the efficient releases of an inert cytotoxic Ru(II) polypyridyl complex and of a luminescent Re(I) tricarbonyl complex using UVA light (one-photon excitation). In addition, in preliminary experiments, we have recently shown that two-photon excitation could be used to release an organic enzyme inhibitor in a cuvette. This technique uses near-IR light irradiation (700-800 nm) to release the molecule of interest instead of the typically used UV light, which is known to damage cells/living organisms over an extended and/or repeated exposure. This wavelength range is also the optimal window for both tissue transparency and classically available laser sources and therefore opens up new avenues for non-invasive imaging or therapy.In this grant extension application, I propose to further extend the scope of the concept developed during the first three years of my SNSF professorship by notably using the two-photon excitation technique instead of one-photon excitation to release specific (metal-based) enzyme inhibitors in living cells. More specifically, specific cellular recognition units (e.g. bombesin, herceptin) will be coupled to two-photon protecting groups (TPPGs) using different ligation techniques (e.g. peptide coupling, Michael addition, etc.) to which known (metal-based) enzyme inhibitors (e.g. histone deacetylase, COX-2, kinase) will be attached. A “prodrug” will hence be formed. Upon light activation, the enzyme inhibitor will be liberated and will therefore be able to turn down the activity of the enzyme (and hence induce cell death).