John C Jewett

John C Jewett

Associate Professor, Chemistry and Biochemistry-Sci
Member of the Graduate Faculty
Associate Professor, BIO5 Institute
Primary Department
Contact
(520) 626-3627

Work Summary

Work Summary

We seek to develop tools and strategies to expedite the understanding and treatment of the dengue virus. These advances will be transferable to other areas of virology and biochemistry. Along these lines, we are engaged in three core synergistic projects to answer the following questions: (1) Do unnatural metabolites incorporated into DENV serve as reporters for host-pathogen interactions? (2) What are the host-pathogen interactions in DENV that are targetable for diagnosis or treatment? (3) Is there a chemical reaction between two small molecules that reports on the interaction between DENV and host proteins?

Research Interest

Research Interest

Our goal is to merge the fields of synthetic organic chemistry with virology. We develop new reactions (and re-appropriate old ones) to gain insight into how viruses infects new host cells. Additionally, we are working to develop new methods to probe protein-protein interactions through the use of small molecules.Viruses can rapidly evolve and new tools are required to meet this ever-changing threat. While vaccinations have tamed many historically deadly viral diseases, there are still rogue viruses for which no vaccination strategy is available. Dengue virus (DENV), the virus that is responsible for dengue fever, hemorrhagic fever, and shock syndrome, is one such pathogen. The WHO estimates that the mosquito-borne pathogen infects over 50 million people each year. With a rapid increase in severe, potentially fatal, disease forms, DENV poses a significant risk to the 2.5 billion people who live in DENV endemic regions.

Publications

Gálvez, E., Romea, P., Urpí, F., Jewett, J. C., & Rawal, V. H. (2009). Preparation of (S)-4-Isopropyl-N-propanoyl-1,3-thiazolidine-2-thione. Organic Syntheses, 86, 70-80.
Martinez-Ariza, G., Mehari, B. T., Pinho, L., Foley, C., Day, K., Jewett, J. C., & Hulme, C. (2017). Synthesis of fluorescent heterocycles via a Knoevenagel/[4+1]-cycloaddition cascade using acetyl cyanide. ORGANIC & BIOMOLECULAR CHEMISTRY, 15(29), 6076-6079.
Jewett, J. C., & Rawal, V. H. (2007). Total synthesis of pederin. Angewandte Chemie - International Edition, 46(34), 6502-6504.

PMID: 17645272;Abstract:

(Chemical Equation Presented) Blisteringly fast: The potent cytotoxic blistering agent pederin has been synthesized (see scheme). The synthesis is diastereoselective and concise (just 12 steps for the longest linear sequence), and features a formal hetero-Diels-Alder reaction of a hindered diene, a Mukaiyama-Michael reaction to set two additional stereocenters, and a Curtius rearrangement to stereospecifically introduce the aminal functionality. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

Jewett, J. C., & Bertozzi, C. R. (2010). Cu-free click cycloaddition reactions in chemical biology. Chemical Society Reviews, 39(4), 1272-1279.

PMID: 20349533;PMCID: PMC2865253;Abstract:

Bioorthogonal chemical reactions are paving the way for new innovations in biology. These reactions possess extreme selectivity and biocompatibility, such that their participating reagents can form covalent bonds within richly functionalized biological systems - in some cases, living organisms. This tutorial review will summarize the history of this emerging field, as well as recent progress in the development and application of bioorthogonal copper-free click cycloaddition reactions. © 2010 The Royal Society of Chemistry.

Guzman, L. E., Kimani, F. W., & Jewett, J. C. (2016). Protecting Triazabutadienes To Afford Acid Resistance. Chembiochem : a European journal of chemical biology, 17(23), 2220-2222.

Recent work on triazabutadienes has shown that they have the ability to release aryl diazonium ions under exceptionally mild acidic conditions. There are instances that require that this release be prevented or minimized. Accordingly, a base-labile protection strategy for the triazabutadiene is presented. It affords enhanced synthetic and practical utility of the triazabutadiene. The effects of steric and electronic factors in the rate of removal are discussed, and the triazabutadiene protection is shown to be compatible with the traditional acid-labile protection strategy used in solid phase peptide synthesis.