Activity-Based Proteomics

Bioconjugation Chemistry for Single-Atom Signaling and Redox Drug Discovery

We are establishing the area of single-atom signaling, focusing on the study of reversible interconversion of methionine and methionine sulfoxide sites in proteins by adding or removing a single oxygen atom. We develop activity-based proteomics probes to identify new targets of methionine modification as well as writers and erasers that regulate their single-atom biology. These chemical tools also reveal new ligandable hotspots for undruggable protein targets and pathways to accelerate the development of next-generation precision medicines that target redox disease vulnerabilities in cancer and neurodegeneration.

Related Publications

• Bioconjugation Methods
• Single-Atom Signaling
• Drug Discovery and Diagnostic Platforms

Bioconjugation Methods

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  Oxidative cyclization reagents reveal tryptophan cation–π interactions

  249

  Xie, X., Moon, P. J., Crossley, S. W. M., Bischoff, A. J., He, D., Li, G., Dao, N., Gonzalez-Valero, A., Reeves, A. G., McKenna, J. M., Elledge, S. K., Wells, J. A., Toste, F. D., & Chang, C. J.

  Nature. 2024, 627, 1-8

• 

  A Physical Organic Approach to Tuning Reagents for Selective and Stable Methionine Bioconjugation

  191

  Christian, A. H.; Jia, S.; Cao, W.; Zhang, P.; Meza, A. T.; Sigman, M. S.; Chang, C. J.; Toste, F. D.

  J. Am. Chem. Soc. 2019, 141, 12657-12662

• 

  Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation

  186

  Jia, S.; He, D.; Chang, C. J.

  J. Am. Chem. Soc. 2019, 141, 7294-7301

• 

  Redox-based reagents for chemoselective methionine bioconjugation

  162

  Lin, S.; Yang, X.; Jia, S.; Weeks, A. M.; Hornsby, M.; Lee, P. S.; Nichiporuk, R. V.; Iavarone, A. T.; Wells, J. A.; Toste, F. D.; Chang, C. J.

  Science 2017, 355, 597-602

Single-Atom Signaling

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  Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism

  248

  Pham, V. N.; Bruemmer, K. J.; Toh, J. D.; Ge, E. J.; Tenney, L.; Ward, C. C.; Dingler, F. A.; Millington, C. L.; Garcia-Prieto, C. A.; Pulos-Homes, M. C.; Ingolia, N. T.; Bontel, L. B.; Esteller, M.; Patel, K. J.; Nomura, D. K.; Chang, C. J.

  Science 2023, 382, 1-10

  Related articles

  What is Epigenetics: Unveiling the Epigenetic Impact of Formaldehyde: A Hazardous Environmental Pollutant

  Berkeley News: Formaldehyde, a carcinogen, is also used by the body to regulate our genes.

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  Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis

  228

  He, D.; Feng, H.; Sundberg, B.; Yang, J.; Powers, J.; Christian, A. H.; Wilkinson, J. E.; Monnin, C.; Avizonis, D.; Thomas, C. J.; Freidman, R. A.; Kluger M. D.; Hollingsworth, M. A.; Grandgenett, P. M.; Klute, K. A.; Toste, D. F.; Chang, C. J; Chio, I. I. C.

  Mol. Cell 2022, 82, 3045-3060

Drug Discovery and Diagnostic Platforms

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  An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4

  235

  Gonzalez-Valero, A.; Reeves, A. G.; Page, A. C. S.; Moon, P. J.; Miller, E.; Coulonval, K.; Crossley, S. W. M.; Xie, X.; He, D.; Musacchio, P. Z.; Christian, A. H.; McKenna, J. M.; Lewis, R. A.; Fang, E.; Dovala, D.; Yipin, L.; McGregor, L. M.; Schirle, M.; Tallarico, J. A.; Roger, P. P.; Toste, F. D., Chang, C. J.

  J. Am. Chem. Soc. 2022, 144, 22890-22901

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  An Activity-Based Methionine Bioconjugation Approach To Developing Proximity-Activated Imaging Reporters

  196

  Ohata, J.; Krishnamoorthy, L.; Gonzalez, M. A.; Xiao, T.; Iovan, D. A.; Toste, F. D.; Miller, E. W.; Chang, C. J.

  ACS Cent. Sci. 2020, 6, 32-40