Jacob Goldberg

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Jacob Goldberg

Assistant Professor of Chemistry

Department/Office Information

105 Wynn Hall

Synthetic chemistry provides unparalleled freedom for the design of probes to study complex biological systems. Because the electronic and reactive properties of small molecules are easily tuned, custom probes have proven to be of great value not only for solving intricate biological problems, but also for the development of new research approaches for understanding health and treating disease. Although significant progress has been made on many fronts using these tools and other techniques, many challenges remain with respect to improving the selectivity, sensitivity, and activity of probes for diverse applications, ranging from the fundamental biochemistry of posttranslational modifications to signal transduction in neural networks. Research in the Goldberg laboratory focuses on the design and application of new chemical tools to overcome these obstacles.

Students working on these research projects are given broad exposure to many techniques from the fields of biophysical chemistry and chemical biology, including chemical synthesis, peptide synthesis, steady state and time resolved optical spectroscopy, photochemistry, and protein expression and purification.

Ƶ undergraduates interested in joining the laboratory are encouraged to discuss possible research opportunities with Professor Goldberg.

  • University of Pennsylvania, PhDin Chemistry (2013)
  • Dartmouth College, ABin Biophysical Chemistry and History (2007)
  • Ƶ, Assistant Professor (2019-present)
  • Ƶ, Visiting Assistant Professor (2017-2019)
  • Massachusetts Institute of Technology, Postdoctoral Research Fellow (2013 – 2017)

Chemical biology, bioinorganic chemistry, molecular biophysics; synthesis and application of chemical probes to study protein structure, function, and dynamics; metalloneurochemistry

Ultra-rapid Electrophilic Cysteine Arylation
Bradley M. Lipka, Daniel S. Honeycutt, Gregory M. Bassett, Taylor N. Kowal, Max Adamczyk, Zachary C. Cartnick, Vincent M. Betti, Jacob M. Goldberg, and Fang Wang
J. Am. Chem. Soc. 145,23427–23432 (2023) DOI:

Mobile zinc as a modulator of sensory perception
Jacob M. Goldberg andStephen J. Lippard
FEBS Lett. 597, 151–165 (2023) DOI:

Rapid Electrophilic Cysteine Arylation with Pyridinium Salts
Bradley M. Lipka, Vincent M. Betti, Daniel S. Honeycutt, Daniel L. Zelmanovich, Max Adamczyk, Ruojun Wu, Harrison S. Blume, Caitlin A. Mendina, Jacob M. Goldberg, and Fang Wang
Bioconjugate Chem. 33, 2189–2196 (2022) DOI:

Cross-α/β polymorphism of PSMα3 fibrils
Olivia M. Cracchiolo, Dean N. Edun, Vincent M. Betti, Jacob M. Goldberg, and Arnaldo L. Serrano
Proc. Natl. Acad. Sci. U. S. A. 119, e2114923119 (2022) DOI:

Mechanisms Underlying Long-Term Synaptic Zinc Plasticity at Mouse Dorsal Cochlear Nucleus Glutamatergic Synapses
Nathan W. Vogler, Vincent M. Betti, Jacob M. Goldberg and Thanos Tzounopoulos
J. Neurosci. 40, 4981-4996 (2020) DOI:

Native Zinc Catalyzes Selective and Traceless Release of Small Molecules in β‐Cells
Miseon Lee, Basudeb Maji, Debasish Manna, Sevim Kahraman, Ruth M. Elgamal, Jonnell Small, Praveen Kokkonda, Amedeo Vetere, Jacob M. Goldberg, Stephen J. Lippard, Rohit N. Kulkarni, Bridget K. Wagner, and Amit Choudhary
J. Am. Chem. Soc. 142, 6477−6482 (2020) DOI:

Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular Zn2+allows tracking of lysosomal Zn2+ǴDZ
Yu Han, Jacob M. Goldberg, Stephen J. Lippard, and Amy E. Palmer
Sci. Rep.8, 15034 (2018)DOI:

New Tools Uncover New Functions for Mobile Zinc in the Brain
Jacob M. Goldberg andStephen J. Lippard
Biochemistry57, 3991–3992 (2018)DOI:

Photoactivatable Sensors for Detecting Mobile Zinc
Jacob M. Goldberg, Fang Wang, Chanan D. Sessler, Nathan W. Vogler, Daniel Y. Zhang, William H. Loucks, Thanos Tzounopoulos, and Stephen J. Lippard
J. Am. Chem. Soc.140, 2020–2023(2018)DOI:

CF2H, a Hydrogen Bond Donor
Chanan D. Sessler, Martin Rahm, Sabine Becker, Jacob M. Goldberg, Fang Wang, and Stephen J. Lippard
J. Am. Chem. Soc.139,9325–9332 (2017)DOI:

Challenges and Opportunities in Brain Bioinorganic Chemistry
Jacob M. Goldberg and Stephen J. Lippard
Acc. Chem. Res.50, 577–579 (2017)DOI:

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’
Jacob M. Goldberg, Andrei Loas, and Stephen J. Lippard
Isr. J. Chem.56,791–802 (2016)DOI:

AMPA Receptor Inhibition by Synaptically Released Zinc
Bopanna I. Kalappa, Charles T. Anderson, Jacob M. Goldberg, Stephen J. Lippard, and Thanos Tzounopoulos
Proc. Natl. Acad. Sci. U. S. A.112, 15749–15754 (2015)DOI:

On the use of thioamides as fluorescence quenching probes for tracking protein folding and stability
E. James Petersson, Jacob M. Goldberg, and Rebecca F. Wissner
Phys. Chem. Chem. Phys.16, 6827-6837 (2014)DOI:

Thioamide-Based Fluorescent Protease Sensors

Jacob M. Goldberg, Xing Chen, Nataline Meinhardt, Doron C. Greenbaum, and E. James Petersson
J. Am. Chem. Soc.136, 2086–2093 (2014)DOI:

Efficient Synthesis and In Vivo Incorporation of Acridon-2-ylalanine, a Fluorescent Amino Acid for Lifetime and Förster Resonance Energy Transfer/Luminescence Resonance Energy Transfer Studies
Lee C. Speight, Anand K. Muthusamy, Jacob M. Goldberg, John B. Warner, Rebecca F. Wissner, Taylor S. Willi, Bradley F. Woodman, Ryan A. Mehl, and E. James Petersson
J. Am. Chem. Soc.135, 18806-18814 (2013)DOI:

Thioamide Quenching of Fluorescent Probes through Photoinduced Electron Transfer: Mechanistic Studies and Applications
Jacob M. Goldberg, Solongo Batjargal, Benson S. Chen, and E. James Petersson
J. Am. Chem. Soc.135, 18651-18658 (2013)DOI:

Molecular basis for N-terminal acetylation by the heterodimeric NatA complex
Glen Liszczak, Jacob M. Goldberg, Håvard Foyn, E. James Petersson, Thomas Arnesen, and Ronen Marmorstein
Nat. Struct. Mol. Biol.20, 1098-1105 (2013)DOI:

Native Chemical Ligation of Thioamide-Containing Peptides: Development and Application to the Synthesis of Labeled α-Synuclein for Misfolding Studies
Solongo Batjargal, Yanxin J. Wang, Jacob M. Goldberg, Rebecca F. Wissner, and E. James Petersson
J. Am. Chem. Soc.134, 9172-9182 (2012)DOI:

Minimalist Probes for Studying Protein Dynamics: Thioamide Quenching of Selectively Excitable Fluorescent Amino Acids
Jacob M. Goldberg, Lee C. Speight, Mark W. Fegley, and E. James Petersson
J. Am. Chem. Soc.134, 6088-6091 (2012)DOI:

Thioamide Quenching of Intrinsic Protein Fluorescence
Jacob M. Goldberg, Rebecca F. Wissner, Alyssa M. Klein, and E. James Petersson
Chem. Commun.48,1550-1552 (2012)DOI:

Thioamides as Fluorescence Quenching Probes: Minimalist Chromophores to Monitor Protein Dynamics
Jacob M. Goldberg, Solongo Batjargal, and E. James Petersson
J. Am. Chem. Soc.132, 14718-14720 (2010)DOI:

  • CHEM 101: General Chemistry I
  • CHEM 102: General Chemistry II
  • CHEM 353: Proteins and Nucleic Acids
  • CHEM 385: Biophysical Chemistry Methods
  • CHEM 454: Bioenergetics
  • CHEM 456: Bioinorganic Chemistry
  • CHEM 468: Medicinal Chemistry
  • FSEM 129: Poisons