Special Centre for Molecular Medicine
JAWAHARLAL NEHRU UNIVERSITY
New Delhi-110067
SEMINAR
SPEAKER:
Prof. (Dr.) Christoph Arenz
Managing Director, Institute for Chemistry Humboldt University, Berlin, Germany
on
Targeting Sphingolipid Metabolizing Enzymes - Potential Treatment of COVID-19, Malaria, Leishmaniasis, Hepatitis C and other Infectious Diseases
DATE & TIME: Wednesday, 9th March 2022 at 3:00 PM
VENUE: Seminar Room, Special Centre for Molecular Medicine
Sphingolipids are main lipids of all eukaryotic plasma membranes. However, they have a wider function than just being membrane constituents. Similar to what is known from other lipids (phosphatidyl inositols, arachnoic acid etc) these membrane constituents have vital functions in cellular lipid signaling.[1] In the last years several sphingolipid-related potential drug targets have been identified. Most prominently, the sphingosine-1-phosphate receptor antagonist Fingolimod is the active compound against multiple sclerosis and Novartis’ best selling drug.
Acid sphingomyelinase (ASM), which is a potential target for the treatment of acute inflammatory processes, including acute lung injury (ALI),[2, 3] sepsis[4] has also been shown to be a target in major depression,[5] spreading of melanoma metastases[6] and in COVID-19.[7] There is also a deficiency of this enzyme known, causing Niemann-Pick disease types A/B. We have developed potent inhibitors for this enzyme,[3, 8] including photo-caged inhibitors[9] and FRET probes that can be used from high throughput screening to live cell applications, including fluorescent microscopy and flow cytometry.[10] We have now started to create disease mimicking cells using CRISPR/Cas and apply our FRET probes in phenotypic small molecule screenings using flow cytometry.
What will be not shown in the talk, but is of major interest for us are sphingolipid metabolizing enzymes in infectious diseases,[11] lipid transporting proteins [12] and sphingolipids in diabetes and metabolic Disease. Apart from the sphingolipid field, we are establishing assays for non-coding RNAs like miRNAs and their interaction with RNA binding proteins.[13]
[1] Y. A. Hannun, L. M. Obeid, Nat Rev Mol Cell Biol 2018, 19, 175-191.
[2] R. Goggel, et al, E. Gulbins, S. Uhlig, Nat Med 2004, 10, 155-160.
[3] A. G. Roth, et al., S. Uhlig, C. Arenz, Angew Chem Int Ed Engl 2009, 48, 7560-7563.
[4] H. Y. Chung, et al. R. A. Claus, Mol Med 2016, 22, 412-423.
[5] E. Gulbins, et al, J. Kornhuber, Nat Med 2013, 19, 934-938.
[6] A. Carpinteiro, et al, E. Gulbins, EMBO Mol Med 2015, 7, 714-734.
[7] J. Kornhuber, N. Hoertel, E. Gulbins, Mol Psychiatry 2021.
[8] A. G. Roth, S. Redmer, C. Arenz, Chembiochem 2009, 10, 2367-2374.
[9] K. Prause, et al, C. Arenz, Chem Commun 2020, 56, 14885-14888.
[10] Z. H. Mohamed, et al, C. Arenz, Bioorg Med Chem 2021, 44, 116303; C. Kappe, et al, C. Arenz, Chemistry 2020, 26, 5780-5783; T. Pinkert, et al., C. Arenz, Angew Chem Int Ed 2017, 56, 2790-2794.
[11] S. Koch-Edelmann, et al, Arenz, D. Heuer, Cell Microbiol 2017, 19.
[12] D. Samaha, et al, C. Arenz, Chemistry 2020, 26, 16616-21.
[13] N. Loibl, C. Arenz, O. Seitz, Chembiochem 2020, 21, 2527-2532; B. P. Davies, C. Arenz, Angew Chem Int Ed Engl 2006, 45, 5550-5552.
