Jacob Goldberg

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Jacob Goldberg

Assistant Professor of Chemistry

Department/Office Information

Chemistry

105 Wynn Hall

Contact

jgoldberg@colgate.edu (315) 228-7872

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.

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

University of Pennsylvania, PhD in Chemistry (2013)
Dartmouth College, AB in Biophysical Chemistry and History (2007)

Colgate University, Assistant Professor (2019-present)
Colgate University, 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: 10.1021/jacs.3c10334

Mobile zinc as a modulator of sensory perception
Jacob M. Goldberg and Stephen J. Lippard
FEBS Lett. 597, 151–165 (2023) DOI: 10.1002/1873-3468.14544

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: 10.1021/acs.bioconjchem.2c00419

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: 10.1073/pnas.2114923119

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: 10.1523/JNEUROSCI.0175-20.2020

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: 10.1021/jacs.0c00099

Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular Zn²⁺ allows tracking of lysosomal Zn²⁺ pools
Yu Han, Jacob M. Goldberg, Stephen J. Lippard, and Amy E. Palmer
Sci. Rep. 8, 15034 (2018) DOI: 10.1038/s41598-018-33102-w

New Tools Uncover New Functions for Mobile Zinc in the Brain
Jacob M. Goldberg and Stephen J. Lippard
Biochemistry 57, 3991–3992 (2018) DOI: 10.1021/acs.biochem.8b00108

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: 10.1021/jacs.7b12766

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: 10.1021/jacs.7b04457

Challenges and Opportunities in Brain Bioinorganic Chemistry
Jacob M. Goldberg and Stephen J. Lippard
Acc. Chem. Res. 50, 577–579 (2017) DOI: 10.1021/acs.accounts.6b00561

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: 10.1002/ijch.201600034

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: 10.1073/pnas.1512296112

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: 10.1039/C3CP55525A

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: 10.1021/ja412297x

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: 10.1021/ja403247j

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: 10.1021/ja409709x

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: 10.1038/nsmb.2636

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: 10.1021/ja2113245

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: 10.1021/ja3005094

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: 10.1039/C1CC14708K

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: 10.1021/ja1044924

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