Dr. Christopher Shugrue
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Profile
Research in my laboratory lies at the interface between organic chemistry and chemical biology. We are interested in designing chemical tools for the development of peptide-based medicines. Normally derived from the 20 natural amino acids, peptides are versatile compounds with a growing list of therapeutic applications, including cancer, diabetes, and infections. While peptides are a promising alternative to traditional small molecule medicines, chemical modifications to their natural sequences are often required in order to enhance their therapeutic activity. Performing organic reactions on biomolecules like peptides, however, is challenging. First, peptides are structurally complex, and contain many reactive functional groups. Second, peptides require aqueous solvent to dissolve and function properly. Alternatively, many synthetic methods are incompatible with water and require organic solvents.
My research group is interested in bridging the gap between organic chemistry and chemical biology. We are focused on designing chemical transformations that are capable of modifying peptide medicines in aqueous environments. These aqueous reactions will be applied toward the development of (1) bioconjugation reagents, which enables the attachment of therapeutic cargo onto peptides, and (2) cleavable linkers, which facilitate the delivery and release of peptides in diseased cells. These interdisciplinary projects will not only allow students to contribute to the advancement of peptides therapeutics, but also expose students to current challenges in synthetic methods, bioorganic chemistry, and environmental sustainability.
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Grants and Fellowships
Claude C. Gravatt and Ann S. Gravatt Endowed Fellowship
NIH Postdoctoral Fellow at Massachusetts Institute of Technology
NSF Graduate Research Fellowship
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Presentations
“Development of Phosphothreonine-Embedded Peptides as Brønsted Acid Catalysts in Stereoselective Reductions.” Gordon Research Conference on Stereochemistry Salve Regina University, Newport, RI, 2018
“Phosphothreonine as a Catalytic Residue in Peptide-Catalyzed Asymmetric Transfer Hydrogenations.” 253rd ACS National Meeting San Francisco, CA, 2017
“Substrate Flexibility in Stereoselectively Catalyzed Michael Reactions.” 244th ACS National Meeting San Diego, CA, 2012
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Grants and Fellowships
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Selected Publications
Journal Articles
Tuan, S.; Dieppa-Matos, D.; Zhang, C.; Shugrue, C. R.; Dai, P.; Loas, A.; Pentelute, B. L. An Engineered Reaction Interface for Site-Selective Cysteine Bioconjugation. Chem. Commun. 2021, 57, 3227–3230. DOI: 10.1039/d1cc00095k.
Pomplun, S. J.(+); Shugrue, C. R.(+); Schmitt, A. M.; Schissel, C. K.; Farquhar, C. E.; Pentelute, B. L. Secondary Amino Alcohols: Traceless Cleavable Linkers for Use in Affinity Capture and Release. Angew. Chem. Int. Ed. 2020, 59, 11566–11572. (+ co-first authors). DOI: 10.1002/anie.202003478.
Metrano, A. J.; Chinn, A. J.; Shugrue, C. R.; Stone, E. A.; Kim, B.; Miller, S. J. Asymmetric Catalysis Mediated by Synthetic Peptides, Version 2.0: Expansion of Scope and Mechanisms. Chem. Rev. 2020, 120, 11479–11615. DOI:10.1021/acs.chemrev.0c00523.
Dardir, A. H.; Hazari, N.; Miller, S. J.; Shugrue, C. R. Palladium-Catalyzed Suzuki-Miyaura Reactions of Aspartic Acid Derived Phenyl Esters. Org. Lett. 2019, 21, 5762–5766. DOI: 10.1021/acs.orglett.9b02214. Highlighted in: Synfacts 2019, 15, 1324.
Shugrue, C. R.; Sculimbrene, B. R.; Jarvo, E. R.; Mercado, B. W.; Miller, S. J. Outer-Sphere Control for Divergent Multicatalysis with Common Catalytic Moieties. J. Org. Chem. 2019, 84, 1664–1672. DOI: 10.1021/acs.joc.8b03068.
Featherston, A. L.; Shugrue, C. R.; Mercado, B. Q; Miller, S. J. Phosphothreonine (pThr)– Based Multifunctional Peptide Catalysis for Asymmetric Baeyer–Villiger Oxidations of Cyclobutanones. ACS Catalysis 2019, 9, 242–252. DOI: 10.1021/acscatal.8b04132. Highlighted in: Synfacts 2019, 15, 0303.
Shugrue, C. R.; Featherston, A. L.; Lackner, R. M.; Lin, A.; Miller, S. J. Divergent Stereoselectivity in Phosphothreonine (pThr)-Catalyzed Reductive Aminations of 3- Amidocyclohexanones. J. Org. Chem. 2018, 83, 4491–4504. DOI: 10.1021/acs.joc.8b00207.
Shugrue, C. R.; Miller, S. J. Applications of Non-Enzymatic Catalysts to the Alteration of Natural Products. Chem. Rev. 2017, 117, 11894–11951. Special Issue: Natural Product Synthesis. DOI: 10.1021/acs.chemrev.7b00022.
Alford, J. A.; Abascal, N. C.; Shugrue, C. R.; Colvin, S. M.; Romney, D. K. Miller, S. J. Aspartyl Oxidation Catalysts That Dial In Functional Group Selectivity, along with Regio- and Stereoselectivity. ACS Cent. Sci. 2016, 2, 733–739. DOI: 10.1021/acscentsci.6b00237.
Shugrue, C. R.; Miller, S. J. Phosphothreonine as a Catalytic Residue in Peptide-Mediated Asymmetric Transfer Hydrogenations of 8-Aminoquinolines. Angew. Chem. Int. Ed. 2015, 54, 11173–11176. DOI: 10.1002/anie.201505898.
Klosowski, D. W.; Hethcox, J. C.; Paull, D. H.; Fang, C.; Donald, J. R.; Shugrue, C. R.; Pansick, A. D.; Martin, S. F. Enantioselective Halolactonization Reactions using a BINOL- derived Bifunctional Catalyst: Methodology, Diversification, and Applications. J. Org. Chem. 2018, 83, 5954–5968. Highlighted in: Synfacts 2018, 14, 0790. DOI: 10.1021/acs.joc.8b00490.
Shugrue, C. R.; DeFrancisco, J. R.; Metrano, A. J.; Brink, B. B.; Nomoto, R. S.; Linton, B. R. Detection of Weak Hydrogen Bonding to Fluoro and Nitro Groups in Solution using H/D Exchange. Org. Biomol. Chem. 2016, 14, 2223–2227. DOI: 10.1039/C5OB02360B.
Shugrue, C. R.; Mentzen, H. H.; Linton, B. R. A colorful solubility exercise for organic chemistry. J. Chem. Ed. 2014, 92, 135–138. Cover Article. DOI: 10.1021/ed4005408.
Fang, C.; Paull, D. H.; Hethcox, C. J.; Shugrue, C. R.; Martin, S. F. Enantioselective Iodolactonization of Disubstituted Olefinic Acids Using a Bifunctional Catalyst. Org. Lett. 2012, 14, 6290–6293. DOI: 10.1021/ol3030555.
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