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Annelise E. Barron, Assistant Professor
Department of Chemical Engineering

Northwestern University

E-mail: a-barron@northwestern.edu
Phone: 847-491-2778
Web: http://www.chem-eng.northwestern.edu/Faculty/barron.html

BS, University of Washington
PhD, University of California, Berkeley
NIH-NRSA Postdoctoral Fellow, University of California, San Francisco

Presidential Early Career Award for Scientists and Engineers, 1999
Beckman Young Investigator Award, 1998
Dow Award for Excellence in Teaching, University of California, Berkeley, 1995

Research Areas
The Barron group works in two emerging areas of nanobiotechnology; development of non-natural oligomers that can mimic the structures and functions of small proteins at the nano-scale, and the design of novel materials and strategies for miniaturized genetic analysis devices that serve as "integrated sample preparation platforms" for nanobioassays.

Folding and Self-Assembling Biomimetic Heteropolymers
The group works on the design, synthesis, and biophysical characterization of foldable and self-assembling peptide mimics. Biopolymers, particularly proteins, are a rich, diverse model system from which fundamental biophysical rules for folding and self-assembly can be inferred and applied to the design of non-natural heteropolymeric 'foldamers'. The motivation for these studies is two-fold. First, to attain a better understanding of the extent of generality of the "protein folding" paradigm, by asking the question, "Can any well-designed chain molecule that has a specific sequence and chain length adopt an ordered three-dimensional conformation?" Second, the investigation of the application of non-natural foldamers as biostable therapeutics. The current research efforts focus on a class of peptide mimics called poly-N-substituted glycines, or peptoids. A simple, automated solid-phase protocol to synthesize sequence-specific polypeptoids is used, incorporating chemically diverse sidechains (including the proteinogenic sidechains). Some peptoid sequences are capable of forming stable helical architectures in solution that are similar to those attained by polyproline molecules. The group is studying the structures of these peptoid foldamers in the Keck Facility by many of the same biophysical methods used to characterize folded structure in natural proteins and investigating their application as therapeutics.

Novel Approaches to Micro- and Nanoscale Analysis of DNA
DNA electrophoresis is a technique of immense practical importance in molecular biological and biomedical research. The Barron group is working to invent new strategies and materials for application to DNA analysis by capillary electrophoresis (CE) as well as by electrophoresis on integrated microfluidic devices. In comparison to old-fashioned slab gels, miniaturized electrophoretic devices provide analytical DNA separations (such as DNA sequencing and genotyping) that are much faster, more efficient, and automatable. One current focus is the development of DNA separation matrices that exhibit a temperature-controlled 'viscosity switch' that allows rapid microchannel loading as well as high-resolution DNA sequencing separations. Another subset of the group is working to develop a new DNA sequencing method, End-Labeled Free-Solution Electrophoresis, that is carried out in free solution, without the use of a gel or separation matrix at all. Finally, novel materials and strategies are being designed to enable integrated electrophoretic chips ("e-chips") that can provide multi-step sample preparation and purification for shunting of pure DNA samples to on-chip, nanoscale bioassays.

Related Publications
"Extreme stability of helices formed by water-soluble poly-N-substituted glycines (polypeptoids) with a-chiral side chains," T.J. Sanborn, C.W. Wu, R.N. Zuckermann, A.E. Barron, Biopolymers (2002) 63, 12-20.

"Peptoid oligomers with a-chiral, aromatic sidechains: Effects of chain length on secondary structure," C.W. Wu, T.J. Sanborn, R.N. Zuckermann, and A.E. Barron, J. Am. Chem. Soc., 73, 157-164 (2001).

"Peptoid oligomers with a-chiral, aromatic sidechains: Sequence requirements for the formation of stable peptoid helices," C.W. Wu, T.J. Sanborn, R.N. Zuckermann, A.E. Barron, J. Am. Chem. Soc. (2001) 123, 6778-6784.

"Molar mass profiling of synthetic polymers by free-solution capillary electrophoresis of DNA-polymer conjugates," W.N. Vreeland, C. Desruisseaux, G. Drouin, G. Slater, A.E. Barron, Anal. Chem. (2001) 73, 1795-1803.

"Microchannel DNA sequencing matrices with a thermally controlled 'viscosity switch,'" B.A. Buchholz, E.A.S. Doherty, M. Albarghouthi, F.M. Bogdan, J.M. Zahn, A.E. Barron, Anal. Chem, 73, 157-164 (2001).

"Impact of polymer hydrophobicity on the properties and performance of DNA sequencing matrices for capillary electrophoresis," M.N. Albarghouthi, B.A. Buchholz, E.A.S. Doherty, F.M. Bogdan, H. Zhou, A.E. Barron, Electrophoresis, 22, 737-747 (2001).

"Polymeric Matrices for DNA Sequencing by Capillary Electrophoresis," M.N. Albarghouthi and A.E. Barron, Electrophoresis, 21, 4096-4111 (2000).

"Bioinspired Polymeric Materials: In-between Proteins and Plastics," A.E. Barron and R.N. Zuckermann, Curr. Opin. Chem. Biol., 3, 681-687 (1999).

 
 
 
Figure 1 - The structure of a helical peptoid oligomer with chiral, N-phenylethyl side chains, as determined by 2D-NMR (Armand et al., PNAS USA 95, 4309-4314, 1998) and idealized by molecular mechanics. This is a right-handed heliz with aobut 3 residues/tum and cis-amide bonds, reminiscent of the structure of a polypeptide polyproline tupe I helix. Organosoluble peptoids such as this one are of interest for mimicking antimicrobial peptides and lung surfactant proteins.

 

 
 
     

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