COBRE - 3

The scientific aim of this Center is to develop a deeper understanding of the recognition elements for structural control in macromolecules. Seven specific projects are directed towards elaboration of atomic level interactions among small molecules to proteins to mesoscale assemblies.  These motifs range from macromolecule surfaces, domains, and scaffolds to the functionally significant specific amino acid side chain residues.  All of the projects require detailed information about the functional interplay of structural motifs. Novel and diverse approaches for obtaining such information are being developed.

These projects incorporate both fundamental and applied research components, including the methodology development. Novel design paradigms are being developed for the study of small molecule protein interactions, protein assembly in membrane environments, the construction of artificial glycoprotein scaffolds to display mulitivalent recognition motifs, and preparation of peptide-based biomaterials whose structures and functions are responsive to environmental cues.  Synthetic methodologies are being pursued to prepare non natural amino acids for incorporation into proteins to impart unique structure and function.  Importantly, design principles established with each individual project can be applied across all of the projects to enhance current design strategies and further the general understanding of biomolecular recognition. COBRE will create an expertise base with appropriate infrastructure to address biomedical questions by identifying molecular design principles that bear on the recognition function of biomolecules, and through the synthetic capability to control molecular topology.

The Center of Biomedical Research Excellence (COBRE) was established at the University of Delaware in September 2002 around a core group of faculty in the Departments of Chemistry and Biochemistry, (DCB) and Materials Science and Engineering, (MSE).

Support for the COBRE center is provided by the  National Center for Research Resources (NCRR) of the National Institutes of Health (NIH) by a grant of $9.7 million dollars for five years.                                                                                                                                                     

COBRE-3 FACULTY 

• MAHENDRA JAIN, PROFESSOR, DCB                                                               
  

• NEAL ZONDLO, ASSISTANT PROFESSOR, DCB

• DARRIN POCHAN, ASSOCIATE PROFESSOR, MSE

• JOEL SCHNEIDER, ASSOCIATE PROFESSOR, DCB

• JOSEPH FOX, ASSISTANT PROFESSOR, DCB

• KRISTI KIICK, ASSISTANT PROFESSOR, MSE

• SANDEEP PATEL, ASSISTANT PROFESSOR, DCB

• TATYANA POLENOVA, ASSOCIATE PROFESSOR, DCB

• CHARLES G. ROIRDAN, PROFESSOR, DCB

• STEVEN DAVID BROWN, W F HARRINGTON PROFESSOR, DCB
  

• MICHAEL H. GELB, PROFESSOR, UNIVERSITY OF WASHINGTON

       http://faculty.washington.edu/gelb/

• SHARON L. HAYNIE, ADJUNCT PROFESSOR, UNIVERSITY OF DELAWARE

       http://www1.dupont.com/NASApp/dupontglobal/corp/index.jsp?page=/content/US/en_US/science/haynie.html
       

• LYNN REGAN, PROFESSOR, YALE UNIVERSITY

       http://www.chem.yale.edu/faculty/regan.html
       http://www.csb.yale.edu/people/regan/

• GEORGE ROSE, PROFESSOR, JOHN HOPKINS UNIVERSITY

       www.roselab.jhu.edu

 
Lian-an Liao and  JOSEPH FOX; “ A Copper-Catalyzed Method for the Facially Selective Addition of Grignard Reagents to Cyclopropens” J. Am. Chem. Soc. 2002, 124,14322-14323

JOEL SCHNEIDER; DARRIN POCHAN; Bulent Ozbas; Karthikan Rajagopal; Lisa Pakstis and Juliana Kretsinger “Responsive Hydrogels from the Intramolecular Folding and Self-Assembly of a Designed Peptide” J. Am. Chem. Soc. 2002, 124, 15030-15037

DARRIN POCHAN ;JOEL SCHNEIDER; Juliana Kretsinger; Bulent Ozbas; Karthikan Rajagopal and Lisa Haines, “Thermally Reversible Hydrogels Via Intramolecular Folding and Consequent Self-Assembly of a de novo Designed Peptide” J. Am. Chem. Soc. 2003, 125, 11802.
   
Liao, L.-a.; Zhang. F.; Dmintrenko, O.; Bach, R. D.;  JOSEPH FOX; “A Reactivity/Affinity Switch for Parallel Kinetic Resolution: a-Amino Acid Quasienantiomers and the Resolution of Cyclopropene Carboxylic Acids” J. Am. Chem. Soc. 2004, 126, 4490-4491

Liao, L.-a.; Zhang, F.; Yan, N.; Golen, J. A.; JOSEPH FOX; “An Efficient and General Method for Resolving Cyclopropene Carboxylic Acids” Tetrahedron 2004,60, 1803.

JOSEPH M. FOX; Olga Dmitrenko; Lian-an Liao; and Robert D. Bach; “ Computational Studies of Nucleophilic Substitution at Carbonyl Carbon: the SN2 Mechanism versus the Tetrahedral Intermediate in Organic Synthesis” J. Org. Chem. 2004, 69; 7317-7328

Bulent Ozbas; Juliana Kretsinger; Karthikan Rajogopal;JOEL SCHNEIDER; DARRIN POCHAN;
“Salt-Triggered Peptide Folding and Consequent Self-Assembly into Hydrogels with Tunable Modulus” Macromolecules 2004, 37, 7331

Liao, L.-a.; Yan, N.; JOSEPH M. FOX ; “Dianion Approach to Chiral Cyclopropene Carboxylic Acids” Organic Letters 2004; 6; 4937-4939. 

Berger, BW; Gendron, CM; CLIFFORD ROBINSON; Kaler, EW; and Lenhoff, AM.;  “The Role of Protein and Surfactant Interactions in Membrane Protein Crystallization” 2004 (Acta D Crystallography, in press)

Dabeiba Marulanda; Maria Luisa Tasayco; Ann McDermott; Marcela Cataldi; Vilma Arriaran;
TATYANA POLENOVA;“ Magic Angle Spinning Solid-State NMR Spectroscopy for Structural Studies of Protein Interfaces.  Resonance Assignments of Differentially Enriched E.coli Thioredoxin Reassembled by Fragment Complementation” J. Am. Chem. Soc., 2004, 126, (50) pp. 16608-16620

Bulent Ozbas; Karthikan Rajagopal;JOEL SCHNEIDER; DARRIN POCHAN; “Semiflexible Chain Networks Formed via Self-Assembly of beta-hairpin Molecules” Physical Review Letters, 2004, 93, 268106

Tzvetana Lazarova; Krista Brewin; Kristin Stoeber; CLIFFORD ROBINSON; "Characterization of Peptides Corresponding to the Seven Transmembrane Domains of Human Adenosine A2a Receptor"  Biochemistry 2004, 43, 12945-12954

Matt Lamm, Karthikan Rajagopal, JOEL P. SCHNEIDER; DARRIN J. POCHAN; "Laminated Morphology of Non-Twisting Beta-Sheet Fibrils Constructed via Peptide Self-Assembly" J. Am. Chem. Soc. 2005, 127, 16692.

Juliana K. Kretsinger, Lisa Haines, Bulent Ozbas, DARRIN J. POCHAN; JOEL P. SCHNEIDER; "Cytocompatibility of Self-Assembled Beta-Hairpin Peptide Hydrogel Surfaces" Biomaterials 2005, 26, 5177

Damien Thèvenin, Tzvetana Lazarova,1 Matthew F. Roberts, and ;CLIFFORD ROBINSON; "Oligomerization of the fifth transmembrane domain from the adenosine A2A receptor" Protein Science (2005), 14:2177-2186

TATYANA POLENOVA; “Resonance Assignments and Secondary Structure Determination in Uniformly and Differentially Enriched Proteins and Protein Reassemblies by Magic Angle Spinning NMR Spectroscopy” 2004 (NMR Spectroscopy of Biological Solids", Eds.  A. Ramamoorthy, Marcel Dekker Inc. New York, in press)

Xiaozhong Liu and JOSEPH M. FOX; “Enantioselective, Facially-selective Carbomagnesation of Cyclopropenes” J. Am. Chem. Soc. 2006, 128, 5600-5601

Zhang, F. and JOSEPH M. FOX; “Synthesis of Cyclopropene á-Amino Acids by Enantioselective Desymmetrization” Organic Letters, 2006, 8, 2965-8.

Thomas, K. M.; Naduthambi,D.; ZONDLO, N.J.; "Electronic Control of Amide Cis-Trans Isomerism via the Aromatic-Prolyl Interaction," J. Am. Chem. Soc., 2006, 128, 2216-2217.

Bielska, A. A.; ZONDLO, N. J.; "Hyperphosphorylation of tau Induces Local Polyproline II Helix," Biochemistry, 2006, 45, accepted for publication.