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Jetze J. Tepe
Research
Synthetic and Bioorganic Chemistry
(Research Description PDF)
Our research program provides an interdisciplinary blend of synthetic and medicinal chemistry that includes the total synthesis of natural products, the discovery of new reactions, as well as the evaluation for their cellular mechanism and medicinal properties. Natural product synthesis: Natural products are still the primary source for medicines, and marine sponge metabolites represent a highly diverse and complex class of natural products with remarkable biological activities. Members of our lab will develop new heterocyclic methodologies to efficiently access these natural products.1,4,5 Cellular studies in our lab will subsequently be performed to identify the biological target responsible for the exciting biological properties these compounds elicit.2,6,7
Medicinal chemistry: Our medicinal chemistry program is aimed at the development of more drug-like scaffolds containing a skeletal diversity inspired by natural products. One of our biological targets includes the human proteasome.
Cancer research: Inhibition of the proteasome is clinically validated for the treatment of multiple myeloma, however nearly all patients relapse after some time. Our natural productinspired scaffolds elicit a unique mechanism of inhibition of this large protease that overcomes resistance to current cancer therapies.2, 6
Alzheimer’s and related research: In Alzheimer’s disease and related dementias, amyloid oligomers inhibit the activity of the proteasome, resulting in the accumulation, oligomerization and aggregation of disordered proteins such as Aβ, tau and α-synuclein.3 Our research team is exploring the use of small heterocyclic scaffolds to activate a specific sub-complex of the proteasome, the 20S proteasome, to treat these neurodegenerative diseases.7
