James S. NowickProfessor, Chemistry |
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Research Interests |
Organic and Bioorganic Chemistry, Chemical Biology, Biomolecular Nanotechnology | |
| URLs | http://www.chem.uci.edu/people/faculty/jsnowick/ | |
| http://www.chem.uci.edu/~jsnowick/groupweb/ | ||
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Academic Distinctions |
•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 |
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| Appointments |
Postdoctoral Fellow, M. I. T. Joined UCI faculty in 1991 |
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Research Abstract |
Research in the Nowick group involves the design, synthesis, and structural evaluation of molecules that are inspired by proteins. My students and I are developing unnatural building blocks that can be used alone or combined with natural amino acids to make synthetic molecules that mimic some of the structures and interactions of proteins. Students in my group learn state-of-the-art techniques for the synthesis of small molecules and peptides and also learn to study molecular structure, conformation, and interactions using modern NMR spectroscopic and molecular modeling methods. Artificial beta-Sheets. One set of projects focuses on developing molecules that mimic the folding and interaction of protein beta-sheets. beta-Sheets are nearly ubiquitous features of proteins that consist of extended peptide strands that held together in part by a network of hydrogen bonds.  A particularly exciting and important feature of beta-sheets is their ability to interact by means of the unsatisfied hydrogen-bonding valences along their edges. Interactions between the edges of beta-sheets occur widely in proteins and are involved in both normal protein function and in diseases ranging from cancer and AIDs to Alzheimer's and Huntington's disease. Our research group has developed unnatural amino acids such as "Hao" (shown below) that induce mimic the hydrogen-bonding properties of beta-sheets and induce beta-sheet structure and interactions when incorporated into peptides. By studying the structure and interactions of peptides containing unnatural amino acids such as "Hao", we hope to gain insight into beta-sheet interactions between proteins and develop new treatments for diseases.  Nanometer-Scale Amino Acids for Biomolecular Nanotechnology. Proteins get their remarkable properties as receptors, catalysts, and effectors of biological processes in part because their relatively large size (nanometers, rather than angstroms) allows them to grip and engulf other molecules. Dozens or hundreds of naturally occurring alpha-amino acids are required to make up a protein, and it is not generally possible to design functional proteins from scratch in part because of their relatively complexity. With the goal of creating molecules that mimic some of the structures and functions of proteins, our group is developing giant amino acid building blocks, such as the iota-amino acid "Adc" and the theta-amino acid "Abc".  The Suzuki cross-coupling reaction allows us to synthesize a diverse array of Adc and Abc derivatives, bearing amino and carboxyl protecting groups suitable for use in synthesis, as shown in the following equation.  The Adc and Abc building blocks are then used to synthesize nanometer-scale structures designed to mimic or interact with biological macromolecules, and the properties of these structures are probed by NMR spectroscopy and related techniques.  Recent Presentations by Nowick Group Members Other Affiliations Links to Course Web Pages Course Video Lectures on YouTube Link to The UCI Chemistry Outreach Program Web Page
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| Publications |
(Selected Publications) "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. |
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| "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. | ||
| "What I Have Learned by Using Chemical Model Systems to Study Biomolecular Structure and Interactions" Nowick, J. S. Org. Biomol. Chem. 2006, 4, 3869-3885. | ||
| "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. | ||
| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2043 | |
| Last updated | 05/14/2013 | |