John Lukesh

Education

B.S., 2009, University of Wisconsin–Milwaukee
Ph.D., 2014, University of Wisconsin–Madison (Ronald T. Raines)
Postdoctorate, 2014–2017, The Scripps Research Institute (Dale L. Boger)

Research Description

The Lukesh lab uses synthetic organic chemistry in an effort to generate novel redox-active molecules with interesting biological properties. With a broad interest in molecular design and its applications to biology and medicine, we are actively pursuing the following areas of research:

Medicinal Chemistry: Construction of novel selenium-containing scaffolds with useful redox properties and therapeutic applications.

Chemical Biology: Elucidating the roles of hydrogen sulfide—an important signaling molecule expressed in mammalian systems—through molecular design and the development of novel reaction-based probes and donor scaffolds.

Synthetic Methodology Development: New methods involving electrophilic selenium catalysis for accessing privileged heterocyclic scaffolds via key C–C bond forming reactions.

Students participating in this research are exposed to a wide variety of topics and techniques at the ever-widening interface of chemistry and biology.

Publications

10. “Selective Staining and Quantification of Intracellular Lipid Droplets with CBD-Fluor, a New and Versatile Push-Pull Fluorophore,” Suarez, S. I.; Warner, C. C.; Brown-Harding, H.; Thooft, A. M.; VanVeller, B.; Lukesh, J. C., III. 2019, Doi: 10.26434/chemrxiv.8872634.v1.

9. “Sub-Picomolar Inhibition of HIV-1 Protease with a Boronic Acid,” Windsor, I. W.; Palte, M. J.; Lukesh, J. C., III; Gold, B.; Forest, K. T.; Raines, R. T. J. Am. Chem. Soc. 2018, 140, 14015– 14018. DOI: 10.1021/jacs.8b07366

8. “Vinblastine 20’ Amides: Synthetic Analogs that Maintain or Improve Potency and Simultaneously Overcome Pgp-derived Efflux and Resistance,” Lukesh, J. C., III; Carney, D. W.; Dong, H.; Cross, M.; Shukla, V.; Duncan, K. K.; Yang, S.; Brody, D. M.; Brutsch, M.; Radakovic, A.; Boger, D. L. J. Med. Chem. 2017, 60, 7591–7604. DOI: 10.1021/acs.jmedchem.7b00958

7. “Total Synthesis of a Key Series of Vinblastines Modified at C4 that Define the Importance and Surprising Trends in Activity,” Yang, S.; Kuppusamy, S.; Skepper, C. K.; Barker, T. J.; Lukesh, J. C., III; Brody, D. M.; Brutsch, M.; Boger, D. L. Chem. Sci. 2017, 8, 1560–1569. DOI: 10.1039/C6SC04146A

6. “Ultra-Potent Vinblastines in which Added Molecular Complexity Further Disrupts the Target Tubulin Dimer–Dimer Interface,” Carney, D. W.; Lukesh, J. C., III; Brody, D. M.; Brutsch, M.; Boger, D. L. Proc. Natl. Acad. Sci. USA 2016, 113, 9691–9698. DOI: 10.1073/pnas.1611405113

5. “Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity,” Allemann, O.; Brutsch, M.; Lukesh, J. C., III; Brody, D. M.; Boger, D. L. J. Am. Chem. Soc. 2016, 138, 8376– 8379. DOI: 10.1021/jacs.6b04330

4. “Organocatalysts of Oxidative Protein Folding Inspired by Protein Disulfide Isomerase,” Lukesh, J. C., III; Andersen, K. A.; Wallin, K. K.; Raines, R. T. Org. Biomol. Chem. 2014, 12, 8598–8602.

3. “A Pyrazine Derived Disulfide-Reducing Agent for Chemical Biology,” Lukesh, J. C., III; Wallin, K.; Raines, R. T. Chem. Commun. 2014, 50, 9591–9594.

2. COVER ARTICLE: “Thiols and Selenols as Electron-Relay Catalysts for Disulfide-Bond Reduction,” Lukesh, J. C., III; VanVeller, B.; Raines, R. T. Angew Chem. Int. Ed. 2013, 52, 12901– 12904. (Hot Paper Distinction).

1. “A Potent, Versatile Disulfide-Reducing Agent from Aspartic Acid,” Lukesh, J. C., III; Palte, M. J.; Raines, R. T. J. Am. Chem. Soc. 2012, 134, 4057–4059. (Highlighted in Chemical & Engineering News. 90(10). March 5, 2012). 

Awards and Accomplishments

• Office of Research & Sponsored Programs Pilot Research Grant, $10,000.00 (2018) 
• Top 10 Best Reviewer for Tetrahedron Journals (2015) 
• Sigma-Aldrich Graduate Student Innovation Award (2013) 
• Harry and Helen Cohen Graduate Research Award (2013) 
• HHMI Teaching Fellow (2013) 
• GSFLC Department Travel Grant Award (2013) 
• Tutor of the Year Award, Tutoring and Academic Resource Center, University of Wisconsin– Milwaukee (2009) 
• Outstanding Senior Award, Department of Chemistry, University of Wisconsin–Milwaukee (2009) 
• Outstanding Performance in Analytical Chemistry Award, Department of Chemistry, University of Wisconsin–Milwaukee (2009) 
• Vanselow Award in Physical Chemistry (2009) 
• Durward Layde Memorial Fellowship (2008) 
• Phi Eta Sigma National Honor Society (2005)