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: Development of chemical tools for probing reactive sulfur and selenium species within a biological setting.

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

13. “Illuminating and Alleviating Cellular Oxidative Stress with an ROS-Activated, H₂S-Donating Theranostic,” Zhu, C.; Suarez, S. I.; Lukesh, J. C., III. Tetrahedron Lett. 2021, 69, 152944–152948. https://doi.org/10.1016/j.tetlet.2021.152944

12. “An Innovative Hydrogen Peroxide-Sensing Scaffold and Insight Towards its Potential as an ROS-Activated Persulfide Donor,” Hankins, R. A.; Suarez, S. I.; Kalk, M. A.; Green, N. M.; Harty, M. N.; Lukesh, J. C., III. Angew. Chem. Int. Ed. 2020, 59, 22238-22245. https://doi.org/10.1002/anie.202010530

11. “Highly Selective Staining and Quantification of Intracellular Lipid Droplets with a Compact Push-Pull Fluorophore based on Benzothiadiazole,” Suarez, S. I.; Warner, C. C.; Brown-Harding, H.; Thooft, A. M.; VanVeller, B.; Lukesh, J. C., III. Org. Biomol. Chem. 2020, 18, 495–499. https://doi.org/10.1039/C9OB02486G

10. COVER ARTICLE: “Selenosulfides Tethered to gem-Dimethyl Esters: A Robust and Highly Versatile Framework for H₂S Probe Development,” Suarez, I. S.; Ambrose, R.; Kalk, M. A.; Lukesh, J. C., III. Chem. Eur. J. 2019, 25, 15736–15740. https://doi.org/10.1002/chem.201904133

Prior to WFU

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

• Center for Molecular Signaling Pilot Research Grant Awardee (2020)
• Office of Research & Sponsored Programs Pilot Grant Awardee (2018)
• Sigma-Aldrich Graduate Student Innovation Award (2013)
• Harry and Helen Cohen Graduate Research Award, Department of Chemistry, University of Wisconsin–Madison (2013)
• HHMI Teaching Fellow (2013)
• Outstanding Senior Award, Department of Chemistry, University of Wisconsin–Milwaukee (2009)