Bradley L. Nilsson

Assistant Professor of Chemistry

Ph.D. 2003, University of Wisconsin, Madison

Bioorganic, Protein and Biopolymer Engineering using Organic Synthesis

The Nilsson group has a strong interest in understanding and exploiting the principles of molecular recognition that give rise to the defined structure and function of proteins. Protein structure is determined by noncovalent interactions including hydrogen bonding, electrostatic forces, and Van der Waals interactions. The sum of these noncovalent interactions accounts for the observed tertiary and quaternary structure of proteins. A variety of peptides and proteins are known to undergo aggregation and self-assembly as a result of abnormal folding, a process that is characteristic of amyloid diseases, including Alzheimer’s disease (AD), Parkinson’s disease, and diabetes.

The Nilsson group is studying noncovalent interactions in the context of self-assembled peptides in an effort to elucidate the roles of peptide aggregation in disease. We are specifically focused on three areas of study:

the characterization of noncovalent side-chain interactions that give rise to protein aggregation and fibril formation, with a focus on the Alzheimer’s disease amyloid-β peptide and other self-assembling peptides;
the design of peptides that self-assemble under the control of small molecules or appended oligonucleotide sequences;
the development of new methods for the chemical synthesis of proteins using oligonucleotide-templated strategies.

These research efforts utilize the tools of synthetic chemistry and biology to provide a highly innovative and interdisciplinary approach to the study of amyloid proteins.

Selected Publications

Nilsson, B. L., Overman, L. E., Read de Alaniz, J., Rohde, J. M. "Enantioselective total syntheses of nankakurines A and B: Confirmation of structure and establishment of absolute configuration," J. Am. Chem. Soc. 2008, 130, 11297–11299.

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.

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Professor Nilsson's Contact Information...

Office: Hutchison 417
Phone: (585) 276-3053