Chemistry - The College - Bradley L. Nilsson

Bradley L. Nilsson

Bioorganic, Protein and Biopolymer Engineering using Organic Synthesis

Assistant Professor of Chemistry
Ph.D. 2003, University of Wisconsin, Madison

(585) 276-3053 -- Hutchison 417 Mailing Address

Proteins and oligonucleotides adopt a variety of secondary and tertiary structures. The regulation of these macromolecular structures is of fundamental importance in biological systems. For example, some proteins under allosteric control can adopt multiple conformations in response to the cellular environment with dramatic consequences for the structure and, by extension, the function of the protein. In some cases the structural changes that occur result in activation or deactivation of the protein's catalytic ability. Much current effort is devoted to understanding the relationship between the primary sequence of a biopolymer and its overall structure.

The ribosome is an elegant molecular machine that plays a central role in protein synthesis. It possess both protein and oligonucleotide elements that exist in tandem. Inspired by the ribosome, we are interested in designing oligonucleotide-protein hybrids that will possess novel structural and functional properties. Oligonucleotides hybridize to form double helices in a predictable manner and we will exploit this characteristic in order to use oligonucleotides to control the structure of appended peptides and proteins. For example, many proteins function as dimers and this dimerization is often mediated by the use of leucine zipper motifs. By replacing leucine zippers with oligonucleotide segments it will be possible to create new types of protein dimers with an added element of specificity programmed into dimer formation.

In addition, oligonucleotides and proteins possess an inherent chirality in their overall structure. DNA with its chiral right-handed helicity is an elegant example of chirality in biological systems. In the Nilsson group we also have an abiding interest in catalysis, and we wish to explore the use of chiral designed biopolymers possessing appended functionality as enantioselective catalysts. The structure of the biopolymers will serve as the chiral scaffold to organize the reactants around the reactive functionality. Since most biopolymers are only extensively used in water, these catalysts could represent an interesting platform to further explore enantioselective catalysis in water.

Relevant Publications

Nilsson, B. L., Overman, L. E. "Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction," J. Org. Chem. 2006, 71, 7706-7714.

Schlieve, C. R., Tam, A., Nilsson, B. L., Lieven, C. J., Raines, R. T., Levin, L. A. "Synthesis and characterization of a novel class of reducing agents that are highly neuroprotective for retinal ganglion cells," Experimental Eye Research 2006, 83, 1252-1259.

Soellner, M. B., Nilsson, B. L., Raines, R. T. "Reaction mechanism and kinetics of the traceless Staudinger ligation," J. Amer. Chem. Soc. 2006, 128, 8820-8828.

Nilsson, B. L., Soellner, M. B., Raines, R. T. "Chemical Synthesis of Proteins," Annu. Rev. Biophys. Biomol. Struct. 2005, 34, 91-118.

Soellner, M. B., Dickson, K. A., Nilsson, B. L., Raines R. T. "Site-specific Protein Immobilization Using the Staudinger Ligation," J. Am. Chem. Soc. 2003, 125, 11790-11791.

Nilsson, B. L., Hondal, R. J., Soellner, M. B., Raines, R. T. "Protein Assembly by Orthogonal Chemical Ligation Methods," J. Am. Chem. Soc. 2003, 125, 5268-5269.

Arnold, U., Hinderaker, M. P., Nilsson, B. L., Huck, B. R. "A Semisynthetic Enzyme with a b-Petide Reverse Turn," J. Am. Chem. Soc. 2002, 124, 8522-8523.

Soellner, M. B., Nilsson, B. L; Raines, R. T. "Staudinger Ligation of a-Azido Acids Retains Stereochemistry," J. Org. Chem. 2002, 67, 4993-4996.

Nilsson, B. L., Kiessling, L. L., Raines, R. T. "High Yielding Staudinger ligation of a Phosphinothioester and Azide to Form a Peptide," Org. Lett. 2001, 3, 9-12.

Hondal, R. J., Nilsson, B. L., Raines, R. T. "Selenocysteine in Native Chemical Ligation and Expressed Protein Ligation," J. Am. Chem. Soc. 2001.

Text | Directory | A-Z Index | Contact | Calendar | News | Giving | Emergency Information

©Copyright 2004–2006, The University of Rochester. All rights reserved.