Synthetic and Bioorganic Chemistry

Jetze Tepe

Associate Professor

510 CEM

517-353-0497


Research webpage


Primary Research Area

Organic (Or)

Other Area(s) of Interest

Biological (Bi)

Research

(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

Fig 1

Fig 2

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.

Fig 3

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

Fig 4

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

Fig 5

Selected Publications

  1. Regulation of Autophagic Flux by the 20S proteasome. Cell, Njomen, Evert and Tepe, Jetze, Cell Chemical Biology 2019, in print, CCBIO3321.
  2. Proteasome activation as a new therapeutic approach to target proteotoxic disorders, Njomen, Evert and Tepe, Jetze J., J. Med. Chem. 2019, in print, DOI:10.1021/ acs.jmedchem.9b00101.
  3. Diastereoselective one-pot synthesis of oxazolines using sulfur ylides and acyl imines, Mehedi, Md Shafaat Al and Tepe, Jetze J., J. Organic Chemistry 2019, 84, 7219-7226.
  4. Pipecolic esters as new templates for proteasome inhibition, Giletto, Matthew B; Osmulski, Pawel A.; Jones, Corey L.; Gaczynska Marie E. and Tepe, Jetze J., Org. & Biomol. Chem. 2019, 17, 2734-2746.
  5. Substrate Controlled Regioselective Bromination of 2-Aycl Pyrroles Using Tetrabutyl Ammonium Tribromide (TBABr3), Gao, Shuang, Bethel, Travis K. Kakeshpour T.; Hubbell, Grace E., Jackson, James, E. and Tepe, Jetze J., J. Org. Chem. 2018, 83, 9250-9255. PMID: 29969032
  6. Small Molecule Modulation of Proteasome Assembly, Njomen, Evert; Osmulski, Pawel A.; Jones, Corey L; Lansdell, Theresa A. Gaczynska, Maria E. and Tepe, Jetze J., Biochem. 2018, 57, 4214-4224. PMID: 29897236
  7. Small molecule enhancement of 20S proteasome activity targets intrinsically disordered proteins, Jones, Corey L.; Njomen, Evert; Sjogren B.; Dexheimer, Thomas S. and Tepe, Jetze J. ACS Chem. Biol. 2017, 15;12(9), 2240-2247. PMID: 28719185.

CV

B.S., 1992, Jacksonville Univ.

Ph.D., 1997, Univ. of Virginia

Postdoctoral Research, 1998-2000, Colorado State Univ.

Awards/Honors

2012 Brian D. Novis Senior Award from the International Myeloma Foundation
2010 - 2010 Multiple Myeloma Senior Research Award Multiple Myeloma Research Foundation
2008 - 2008 Multiple Myeloma Senior Research Award Multiple Myeloma Research Foundation
2005 - 2005 Teacher-Scholar Award Michigan State University
2003 Research Scholar Award American Cancer Society
1997 Ph.D. University of Virginia
1997 Alfred Burger Fellowship, Senior Thesis Fellowship University of Virginia
1994 Dean’s Reserve Fellowship University of Virginia
1992 Bachelor of Science Jacksonville University