James S. Nowick

picture of James S. Nowick

Distinguished Professor, Chemistry
School of Physical Sciences


PH.D., Massachusetts Institute of Technology, 1990
A.B., 1985, Columbia University

Phone: (949) 824-6091
Fax: (949) 824-9920
Email: jsnowick@uci.edu

University of California, Irvine
4126 Natural Sciences 1
Mail Code: 2025
Irvine, CA 92697
Research Interests
Organic and Bioorganic Chemistry, Chemical Biology
URLs
Academic Distinctions
•Charles R. Bennett Service Through Chemistry Award from the ACS Orange County Section
•American Chemical Society (ACS) Fellow
•American Association for the Advancement of Science (AAAS) Fellow
•NOGLSTP Scientist of the Year Award
•UCI School of Physical Sciences Award for Outstanding Contributions to Undergraduate Education
•American Chemical Society Arthur C. Cope Scholar Award
•UCI Chancellor's Award for Excellence in Undergraduate Research
•Alfred P. Sloan Research Fellowship
•Camille Dreyfus Teacher-Scholar Award
•Presidential Faculty Fellow
•UCI Award for Outstanding Faculty Contribution to Undergraduate Research
•Arnold and Mabel Beckman Foundation Young Investigator
•National Science Foundation Young Investigator
•American Cancer Society Junior Faculty Research Award
•Camille and Henry Dreyfus Foundation Distinguished New Faculty Award
•National Science Foundation Postdoctoral Fellow
•American Chemical Society Division of Organic Chemistry Graduate Fellow
•National Science Foundation Graduate Fellow
Appointments
Postdoctoral Fellow, M. I. T.

Joined UCI faculty in 1991
Research Abstract

Research in the Nowick group focuses on the chemistry and biology of peptides. Areas of particular interest include understanding molecular basis of amyloid diseases, such as Alzheimer’s disease, and the development of new antibiotics.


The design, synthesis, and study of new molecules is central to our efforts. We use small molecule chemical synthesis, peptide synthesis, and protein expression to create the molecules that we study, and molecular modeling, NMR spectroscopy, and X-ray crystallography to gain insights into their structures and biomolecular interactions. Experiments with mammalian cells and bacteria, as well as fluorescence microscopy help elucidate the biological properties of the molecules that we create, as do some animal-based studies in mice. A particular area of interesting our laboratory is the structures and supramolecular interactions of ß-sheets, which are central to the folding and assembly of the peptides associated with amyloid diseases, such as Alzheimer’s disease, as well as the antibiotic teixobactin.



Our extensive program of research on understanding the molecular basis of amyloid diseases focuses on developing chemical models of the toxic amyloid oligomers associated Alzheimer’s disease and other amyloid diseases. In typical studies, we design peptides derived from Aß and other amyloidogenic peptides and proteins and then study their structures and assembly, as well as their biological properties. Through X-ray crystallography, we have been able to observe the structures of a variety oligomers formed by constrained ß-hairpin peptides derived from key amyloidogenic peptides and proteins. Current efforts seek to correlate these chemical models of amyloid oligomers with biogenic amyloid oligomers found in the brain and to develop antibodies and vaccines to block the neurodegeneration associated with these amyloid oligomers.



In 2015 we became interested in the newly reported antibiotic teixobactin and launched a program of study to learn more about its chemistry and biology. By synthesizing teixobactin analogues and studying their antibiotic activity, we gained new insights into the mechanism of action of teixobactin. Through X-ray crystallography, we discovered that teixobactin forms dimers and higher-order assemblies through ß-sheet formation that can bind to its molecular targets on the cell membrane of Gram-positive bacteria. We are now using what we have learned from teixobactin to design new antibiotics against MRSA, VRE, and other dangerous pathogens.



Students in the Nowick group partake fully of the rich environment of mentorship and training provided by our research laboratory. Graduate students participate in hypothesis generation, data collection, data analysis, and communication through oral and written presentation. Many graduate students choose to mentor undergraduate research students, further enhancing their graduate training while helping to train the next generation. I meet with students individually each week to discuss their results and plans for subsequent experiments. Additional scheduled and ad-hoc meetings occur throughout the week. When students are writing papers for publication, I work closely with them, providing guidance and feedback in the writing process.


My group and I meet collectively on Tuesday afternoons during our weekly group meetings. Our group meetings consist of three formats: research, literature, and workshop. In our research group meetings, students present and discuss their results orally with slides and get feedback and discussion that leads to ideas for future experiments. In our literature group meetings, we discuss important publications from the current literature, with each student making slide presentations on articles. When students are preparing to give talks or engaging in various writing projects, the group often provides feedback and guidance in a workshop format. Through this program of research training, continuing education, and mentorship, students acquire the skills to become successful independent scientists.



Nowick Group Website

Other Affiliations
Chao Family Comprehensive Cancer Center (UCI)
Institute for Genomics and Bioinformatics (UCI)
Alzheimer's Disease Research Center, UCI MIND (UCI)


Course Video Lectures on YouTube
Chem 203. Organic Spectroscopy, Fall 2020
Chem 203. Organic Spectroscopy, Fall 2020 Course Website
Chem 203. Organic Spectroscopy, Fall 2011
Chem 125. Advanced Organic Chemistry
Chem 51A. Organic Chemistry
Chem 51B. Organic Chemistry (Professor David Van Vranken)
Chem 51C. Organic Chemistry
Links to other OpenChemistry Lecture Videos


Scholarly Websites
Organic Spectroscopy Problems
PeptideLinks.net


Link to The UCI Chemistry Outreach Program Web Page

Available Technologies
Publications
(Selected Publications)

"A Tetramer Derived from Islet Amyloid Polypeptide" Wang, Y.; Kreutzer, A. G.; Truex, N.L.; Nowick, J. S. J. Org. Chem. 2017, 82, 7905-7912.
 
"X-ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16–22" Salveson, P. J.; Spencer, R. K.; Kreutzer, A. G.; Nowick, J. S. Org. Lett. 2017, 19, 3462-3465.
 
"X-ray Crystallographic Structure of a Giant Double-Walled Peptide Nanotube Formed by a Macrocyclic β-Sheet Containing Aβ16–22" Chen, K. H.; Corro, K. A.; Le, S. P.; Nowick, J. S. J. Am. Chem. Soc. 2017, 139, 8102-8105.
 
"X-ray Crystallographic Structure of a Teixobactin Analogue Reveals Key Interactions of the Teixobactin Pharmacophore" Yang, H.; Du Bois, D. R.; Ziller, J. W.; Nowick, J. S. Chem. Commun. 2017, 53, 2772-2775.
 
"Stabilization, Assembly, and Toxicity of Trimers Derived from Aβ" Kreutzer, A. G.; Yoo, S.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc 2017, 139, 966-975.
 
"Coassembly of Peptides Derived from β-Sheet Regions of β-Amyloid" Truex, N. L.; Nowick, J. S. J. Am. Chem. Soc 2016, 138, 13891-13900.
 
"Assembly of Peptides Derived from β-Sheet Regions of β-Amyloid" Truex, N. L.; Wang, Y.; Nowick, J. S. J. Am. Chem. Soc 2016, 138, 13882-13890.
 
"Square Channels Formed by a Peptide Derived from Transthyretin" Yoo, S.; Kreutzer, A. G.; Truex, N. L.; Nowick, J. S. Chem. Sci. 2016, 7, 6946–6951.
 
"Elucidation of the Teixobactin Pharmacophore" Yang, H.; Chen, K. H.; Nowick, J. S. ACS Chem. Biol. 2016, 11, 1823–1826.
 
"X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin" Kreutzer, A. G.; Hamza, I. L.; Spencer, R. K.; Nowick, J. S. J. Am. Chem. Soc. 2016, 138, 4634-4642.
 
"X-ray Crystallographic Structure of Oligomers Formed by a Toxic β-Hairpin Derived from α-Synuclein: Trimers and Higher-Order Oligomers" Spencer, R. K.; Kreutzer, A. G.; Salveson, P. J.; Li, H.; Nowick, J. S. J. Am. Chem. Soc. 2016, 138, 4458-4467.
 
"X-ray Crystallographic Structures of Oligomers of Peptides Derived from β2-Microglobulin" Spencer, R. K.; Kreutzer, A. G.; Salveson, P. J.; Li, H.; Nowick, J. S. J. Am. Chem. Soc. 2015, 137, 6304–6311.
 
"A Newcomer's Guide to Peptide Crystallography" Spencer, R.; Nowick, J. S. Israel J. Chem 2015, 55, 698–710.
 
"A Fibril-like Assembly of Oligomers of a Peptide Derived from β-Amyloid" Pham, J. D.; Spencer, R.; Chen, K. H.; Nowick, J. S. J. Am. Chem. Soc. 2014, 136, 12682-12690.
 
 
"Polymorphism of Oligomers of a Peptide from β-Amyloid" Pham, J. D.; Demeler, B.; Nowick, J. S. J. Am. Chem. Soc. 2014, 136, 5432-5442. Spotlight in JACS "Finding the Solution: The Structure of Soluble Amyloid Oligomers"
 
"Mechanism of IAPP Amyloid Fibril Formation Involves an Intermediate with a Transient β-Sheet" Buchanan, L. E.; Dunkelberger, E. B.; Tran, H. Q.; Cheng, P.-N.; Chiu, C.-C.; Cao, P.; Raleigh, D. P.; de Pablo, J. J.; Nowick, J. S.; Zanni, M. T. Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 19285-19290.
 
"Structures of Oligomers of a Peptide from β-Amyloid" Pham, J. D.; Chim, N.; Goulding, C. W.; Nowick, J. S. J. Am. Chem. Soc. 2013, 135, 12460-12467.
 
"Recipe for ß-Sheets: Foldamers Containing Amyloidogenic Peptide Sequences" Spencer, R.; Chen, K. H.; Manuel, G.; Nowick, J. S. Eur. J. Org. Chem. 2013, 3523-3528.
 
"A Hydrophobic Surface is Essential to Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide" Zheng, J.; Baghkhanian, A. M.; Nowick, J. S. J. Am. Chem. Soc. 2013, 135, 6846-6852.
 
"The Supramolecular Chemistry of β-Sheets" Cheng, P.-N.; Pham, J. D.; Nowick, J. S. J. Am. Chem. Soc. 2013, 135, 5477–5492.
 
"Amyloid β-Sheet Mimics that Antagonize Protein Aggregation and Reduce Amyloid Toxicity" Cheng, P.-N.; Liu, C.; Zhao, M.; Eisenberg, D.; Nowick, J. S. Nature Chemistry 2012, 4, 927-933.
 
"Out-of-Register β-Sheets Suggest a Pathway to Toxic Amyloid Aggregates" Liu, C.; Zhao, M.; Jiang, L.; Cheng, P.-N.; Park, J.; Sawaya,. M. R.; Pensalfini, A.; Gou, D.; Berk, A. J.; Glabe, C. G.; Nowick, J. S.; Eisenberg, D. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 20913-20918.
 
"Heterodivalent Linked Macrocyclic β-Sheets with Enhanced Activity against Aβ Aggregation: Two Sites are Better than One." Cheng, P.-N.; Spencer, R.; Woods, R. J.; Glabe, C. G.; Nowick, J. S. J. Am. Chem. Soc. 2012, 133, 14179-14184.
 
"Giant Macrolactams Based on β-Sheet Peptides" Cheng, P.-N.; Nowick, J. S. J. Org. Chem. 2011, 76, 3166-3173.
 
"Characteristics of Amyloid-Related Oligomers Revealed by Crystal Structures of Macrocyclic β-Sheet Mimics" Liu, C.; Sawaya, M. R.; Cheng, P.-N.; Zheng, J.; Nowick, J. S.; Eisenberg, D. J. Am. Chem. Soc. 2011, 133, 6736-6744.
 
"Macrocyclic β-Sheet Peptides that Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide" Zheng, J.; Liu, C.; Sawaya, M. R.; Vadla, B.; Khan, S.; Woods, R. J.; Eisenberg, D.; Goux, W. J.; Nowick, J. S. J. Am. Chem. Soc. 2011, 133, 3144-3157.
 
"X-ray Crystallographic Structure of an Artificial β-Sheet Dimer" Khakshoor, O.; Lin, A. J.; Korman, T. P.; Sawaya, M. R.; Tsai, S.-C.; Eisenberg, D.; Nowick, J. S. J. Am. Chem. Soc. 2010, 132, 11622-11628.
 
"Nanometer-Scale Water-Soluble Macrocycles from Nanometer-Sized Amino Acids" Gothard, C. M.; Nowick, J. S. J. Org. Chem. 2010, 75 1822-1830.
 
"Use of Disulfide “Staples” To Stabilize β-Sheet Quaternary Structure" Khakshoor, O.; Nowick, J. S. Org. Lett. 2009, 11, 3000-3003.
 
"A New Artificial β-Sheet that Dimerizes through Parallel β-Sheet Interactions" Levin, S.; Nowick, J. S. Org. Lett. 2009, 11, 1003-1006.
 
"Exploring β-Sheet Structure and Interactions with Chemical Model Systems" Nowick, J. S. Acc. Chem. Res. 2008, 41, 1319-1330.
 
"Functionalized Analogues of an Unnatural Amino Acid that Mimics a Tripeptide β-Strand" Khasanova, T. V.; Khakshoor, O.; Nowick, J. S. Org. Lett. 2008, 10, 5293-5296.
 
"An Artificial β-Sheet That Dimerizes through Parallel β-Sheet Interactions" Levin, S.; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 13043-13048.
 
"Nanometer-Sized Amino Acids for the Synthesis of Nanometer-Scale Water-Soluble Molecular Rods of Precise Length" Gothard, C. M.; Rao, N. A.; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 7272-7273.
 
"Macrocyclic β-Sheet Peptides that Mimic Protein Quaternary Structure through Intermolecular β-Sheet Interactions" Khakshoor, O.; Demeler, B.; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 5558-5569.
 
"Cyclic Modular β-Sheets" Woods, R. J.; Brower, J. O.; Castellanos, E.; Hashemzadeh, M.; Khakshoor, O.; Russu, W. A.; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 2548-2558.
 
"A New Class of Macrocyclic Receptors from iota-Peptides" Kang, S.-W. Gothard, C. M.; Maitra, S.; Atia-tul-Wahab; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 1486-1487.
 
 
"The Absence of Favorable Aromatic Interactions between β-Sheet Peptides" Chung, D. M.; Dou, Y.; Baldi, P.; Nowick, J. S. J. Am. Chem. Soc. 2005, 127, 9998-9999.
 
"Enantioselective Molecular Recognition between β-Sheets" Chung, D. M.; Nowick, J. S. J. Am. Chem. Soc. 2004, 126, 3062-3063.
 
"DSA: A New Internal Standard for NMR Studies in Aqueous Solution", Nowick, J. S.; Khakshoor, O.; Hashemzadeh, M.; Brower, J. O. Org. Lett. 2003, 5, 3511-3513.
 
"Sequence-Selective Molecular Recognition Between β-Sheets", Nowick, J. S.; Chung, D. M. Angew. Chem., Int. Ed. Engl. 2003, 42, 1765-1768.
 
"A Ribozyme with Michaelase Activity: Synthesis of the Substrate Precursors" Eisenführ, A.; Arora, P. S.; Sengle, G.; Takaoka, L. R.; Nowick J. S.; Famulok, M. Bioorg. Med. Chem. 2003, 11, 235-249.
 
"A New Turn Structure for the Formation of β-Hairpins in Peptides", Nowick, J. S.; Brower, J. O. J. Am. Chem. Soc. 2003, 125, 876-877.
 
"Methylglyoxal Synthetase, enol-Pyruvaldehde, Glutathione, and the Glyoxalase System" Rose, I. A.; Nowick, J. S. J. Am. Chem. Soc. 2002, 124, 13047-13052.
 
"An Unnatural Amino Acid that Induces β-Sheet Folding and Interaction in Peptides", Nowick, J. S.; Lam, K. S.; Khasanova, T. V.; Kemnitzer, W. E.; Maitra, S.; Mee, H. T.; Liu, R. J. Am. Chem. Soc. 2002, 124, 4972-4973.
 
"Three-Stranded Mixed Artificial β-Sheets" Nowick, J. S.; Smith, E. M.; Ziller, J. W.; Shaka, A. J. Tetrahedron 2002, 58, 727-739.
 
"A Triply Templated Artificial β-Sheet", Nowick, J. S.; Cary, J. M.; Tsai, J. H. J. Am. Chem. Soc. 2001, 123, 5176-5180.
 
"Novel RNA Catalysts for the Michael Reaction" Sengle, G.; Eisenführ, A.; Arora, P. S.; Nowick, J. S.; Famulok, M. Chemistry & Biology 2001, 8, 459-473.
 
"An Unnatural Amino Acid that Mimics a Tripeptide β-Strand and Forms β-Sheetlike Hydrogen-Bonded Dimers", Nowick, J. S.; Chung, D. M.; Maitra, K.; Maitra, S.; Stigers, K. D.; Sun, Y. J. Am. Chem. Soc. 2000, 122, 7654-7661.
 
"Fmoc*: A More Soluble Analogue of the 9-Fluorenylmethoxycarbonyl Protecting Group", Stigers, K. D.; Koutroulis, M. R.; Chung, D. M.; Nowick, J. S. J. Org. Chem. 2000, 65, 3858-3860.
 
"β-Sheet Interactions Between Proteins", Maitra, S.; Nowick, J. S. In: The Amide Linkage: Structural Significance in Chemistry, Biochemistry, and Materials Science; Greenberg, A.; Breneman C. M.; Liebman, J. F., Eds.; Wiley: New York, 2000; Chapter 15.
 
"A Chemical Model of a Protein β-Sheet Dimer", Nowick, J. S.; Tsai, J. H.; Bui, Q.-C. D.; Maitra, S. J. Am. Chem. Soc. 1999, 121, 8409-8410.
 
"Chemical Models of Protein β-Sheets", Nowick, J. S. Acc. Chem. Res. 1999, 32, 287-296.
 
"An Efficient Synthesis of N,N'-Linked Oligoureas" Wilson, M. E.; Nowick, J. S. Tetrahedron Lett. 1998, 39, 6613-6616.
 
"The Propensities of Amino Acids to Form Parallel β-Sheets", Nowick, J. S.; Insaf, S. J. Am. Chem. Soc. 1997, 119, 10903-10908.
 
"Solid-Phase Synthesis of Artificial β-Sheets", Holmes, D. L.; Smith, E. M.; Nowick, J. S. J. Am. Chem. Soc. 1997, 119, 7665-7669.
 
"An Extended β-Strand Mimic for a Larger Artificial β-Sheet", Nowick, J. S.; Pairish, M.; Lee, I. Q.; Holmes, D. L.; Ziller, J. W. J. Am. Chem. Soc. 1997, 119, 5413-5424.
 
"Synthesis of Peptide Isocyanates and Isothiocyanates", Nowick, J. S.; Holmes, D. L.; Noronha, G.; Smith, E. M.; Nguyen, T. M.; Huang, S.-L. J. Org. Chem. 1996 , 61, 3929-3934. Addendum: J. Org. Chem. 1998, 63, 9144.
 
"A Coordinated Chemistry Outreach Program that Reaches Thousands of High School Students", Waldman, A. S.; Schechinger, L.; Nowick, J. S. J. Chem. Educ. 1996, 73, 762-764.
 
"An Artificial β-Sheet Comprising a Molecular Scaffold, a β-Strand Mimic, and a Peptide Strand", Nowick, J. S.; Holmes, D. L.; Mackin, G.; Noronha, G.; Shaka, A. J.; Smith, E. M. J. Am. Chem. Soc. 1996, 118, 2764-2765.
 
"Triurea Derivatives of Diethylenetriamine as Potential Templates for the Formation of Artificial β-Sheets", Nowick, J. S.; Mahrus, S.; Smith, E. M.; Ziller, J. W. J. Am. Chem. Soc. 1996, 118, 1066-1072.
 
"Molecular Scaffolds 3. An Artificial Parallel β-Sheet", Nowick, J. S.; Smith, E. M.; Noronha, G. J. Org. Chem. 1995, 60, 7386-7387.
Last updated
09/22/2021