Forschung / Research
We are interested in controllable / switchable chemical catalysts. The control can be achieved by applying physical (light) or (bio)chemical (reactive oxygen species, metal ions etc) factors. These catalysts are used to regulate / affect / monitor biochemical processes / molecules in live cells.
In particular, we work on the following projects:
MONITORING NUCLEIC ACIDS IN LIVE CELLS
CANCER SPECIFIC PRODRUGS
„CAGED“ REAGENTS RESPONSIVE TO RED LIGHT
CHEMISTRY IN LIVE CELLS (Project within Emerging Field Initiative of FAU)
1. Monitoring nucleic acids in live cells: we develop photochemical catalytic reactions, which are controlled by nucleic acids and triggered on by non-toxic red light, and apply them for quantitative and sequence specific detection of nucleic acids in live cells. These activities are supported by German Research Foundation.
- Pieper, H.; Halbig, C. E.; Kovbasyuk, L.; M. R. Filipovic, Eigler, S.;* Mokhir, A.* Oxo-functionalized graphene as cell membrane carrier of nucleic acids probes controlled by aging. Chem. Eur. J., 2016, 22(43), 15389-15395.
- Beierlein, F. R.;* Palomo, M. P.; Sharapa, D. I.; Zozulia, O.; Mokhir, A.; Clark, T. DNA-dye-conjugates: conformation and spectra of fluorescence probes. PLOS ONE, 2016, 11(7), e0160229.
- Schikora, M.; Mokhir, A.* Cu(II)-complexes as quenchers of photocatalytic activity of visible light-absorbing photosensitizers: an application in detection of nucleic acids. Inorg. Chim. Acta, 2016, (special issue on „Metal-nucleic acid interactions – state of the art“). 452, 118-124.
- Mokhir, A.* Chemical reactions controlled by nucleic acids. Book chapter (DNA in Supramolecular Chemistry and Nanotechnology, John Wiley & Sons, Ltd, Eds. E. Stulz and G. H. Clever). 2015. ISBN: 978-1-118-69686-6.
- Schikora, M., Dutta, S.; Mokhir, A.* Nucleic acid – specific photoactivation of oligodeoxyribonucleotides labeled with deuterated dihydro-N,N,N‘,N‘-tetramethylrhodamine using green light, Histochem. Cell Biol., (2014), 142(1), 103-111.
- Dutta, S.; Fülöp, A.; Mokhir, A.* A fluorogenic, catalytic, photochemical reaction for amplified detection of nucleic acids, Bioconjugate Chemistry, (2013), 24(9), 1533-1542.
- Dutta, S.; Flottmann, B.; Heilemann, M.; Mokhir, A.* Hybridization and reaction-based, fluorogenic nucleic acid probes, Chem. Comm. (2012), 47, 9664-9666.
- Arian, D.; Kovbasyuk, L.; Mokhir, A.* Control of the Photocatalytic Activity of Bimetallic Complexes of Pyropheophorbide-a by Nucleic Acids, Inorg. Chem., (2011), 50(23), 12010-12017.
- Arian, D.; Kovbasyuk, L.; Mokhir, A.* 1,9-Di(alkoxy)anthracene as a Singlet Oxygen-Sensitive Linker, J. Am. Chem. Soc. (2011), 133(11), 3972-3980.
- Dutta, S.; Mokhir, A.* An autocatalytic chromogenic and fluorogenic photochemical reaction controlled by nucleic acids, Chem. Comm. (2011), 47(4), 1243-1245.
Landesstiftung BW (info-document, page 54),
2. Cancer specific prodrugs: we develop aminoferrocene-based prodrugs, which are activated specifically at cancer-specific conditions (high concentration of reactive oxygen species, ROS), with formation of quinone methides and aminoferrocenes. The former products inhibit the antioxidant system of cells and the latter catalyze generation of ROS. The dual synergistic effect of these products lead to cancer cell death. Since the prodrugs are not activated in normal cells, they exhibit low to no toxicity. These activities are supported by German Research Foundation.
- Reshetnikov, V.; Daum, S.; Mokhir, A.* Cancer specific, intracellular, reductive activation of anticancer Pt(IV)-prodrugs. Chem. Eur. J., 2017, accepted.
- Kinski, E.; Marzenell, P.; Hofer, W.; Hagen, H.; Raskatov J. A.; Knaup, K. X.; Zolnhofer, E. M.; Meyer, K.; Mokhir, A.* 4-Azidobenzyl ferrocenylcarbamate as an anticancer prodrug activated at reductive conditions. J. Inorg. Biochem. 2016, 160, 218-224 (special issue: Metallodrugs/COST action).
- Schikora, M.; Reznikov, A.; Chaykovskaya, L.; Sachinska, O.; Polyakova, L.; Mokhir, A.* Activity of aminoferrocene-based prodrugs against prostate cancer. Bioorg. Med. Chem. Lett. (2015), 25(17), 3447-3450.
- Daum, S.; Chekhun, V.; Todor, I.; Lukianova, N.; Shvets, Y.; Sellner, L.; Putzker, K.; Lewis, J.; Zenz, T.; Graaf, I.; Groothuis, G.; Casini, A.; Zozulia, O.; Hampel, F.; Mokhir, A.* Improved synthesis of N-benzylaminoferrocene-based prodrugs and evaluation of their toxicity and antileukemic activity. J. Med. Chem. (2015), 58(4), 2015-2024.
- Marzenell, P.; Hagen, H.; Sellner, L.; Zenz, T.; Grinyte, R.; Pavlov, V.; Daum, S.; Mokhir, A.* Aminoferrocene-based prodrugs and their effects on human normal and cancer as well as bacterial cells, J. Med. Chem., (2013), 56(17), 6935-6944.
- Hagen, H.; Marzenell, P.; Jentzsch, E.; Wenz, F.; Veldwijk, M. R.; Mokhir, A.* Aminoferrocene-Based Prodrugs Activated by Reactive Oxygen Species, J. Med. Chem., (2012), 55(2), 924-934.
3. “Caged” reagents for spatial and temporal control of gene expression and RNA interference in cells. We develop the reagents (siRNAs, miRNAs etc), which are activated by nontoxic red light (> 600 nm).
- Meyer, A.; Schikora, M.; Starkuvienne, V.; Mokhir, A.* Red light activated „caged“ reagents for micro RNA research. Photochem. Photobiol. Sci., 2016, 15(9), 1120-1123.
- Meyer, A.; Schikora, M.; Mokhir, A.* Red light controlled polymerase chain reaction. Chem. Comm. (2015), 51, 13324-13326.
- Meyer, A.; Mokhir, A.* RNA interference controlled by light of variable wavelength. Angew. Chem. Int. Ed., (2014), 53(47), 12840-12843.
- König, S.; Mokhir, A.* „Caged“ peptide nucleic acids activated by red light in a singlet oxygen-mediated process, Bioorg. Med. Chem. Lett., (2013), 23(24), 6544-6548.
Friedrich-Alexander-University of Erlangen-Nürnberg
4. Chemistry in live cells: An interdisciplinary team covering fields of organic chemistry (Mokhir, Schatz, Tsogoeva, Jux), pharmacetical chemistry (Heinrich), physical chemistry (Guldi, Heilemann), theoretical chemistry (Beierlein, Clark) and medicine (Prante) is working since 01.01.2017 on the develpment of chemical bond-forming reactions (C-O, C-S, C-Se, C-C), which are compatible with live cells. These reactions should lead to formation of either drugs or easily detectable (e.g. fluorescent, radioactive) compounds. The results, which can be obtained in this project, can potentially lead to new treatment methods for diseases like cancer and chronic inflammation as well as to novel diagnostic tools. The project is initially funded for two years by Friedrich-Alexander-Universität Erlangen-Nürnberg in the framework of Emerging Field Initiative.