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Scripps Research Joint Appointments

Department of Cell and Molecular Biology
Faculty, Kellogg School of Science and Technology

Research Focus

Development & Utilization of Methods to Incorporate Unnatural Chemical Groups into Proteins

We have developed a chemical approach for the production of the large polypeptide chains that comprise protein molecules, enabling us to change the structure of a protein in ways impossible by natural means. We use solid phase peptide synthesis to generate peptides up to ~50 amino acids in length and then assemble them using chemoselective reactions to make proteins up to ~150 amino acids in length. This—chemical ligation—approach greatly facilitates the synthesis of proteins of moderate size and has opened the world of proteins to the synthetic tools of organic chemistry. Chemical ligation can be extended to biologically expressed proteins enabling the semisynthesis of proteins of unlimited size that contain fluorophores or cross-linking agents at defined positions. Our goal is to introduce non-coded amino acids and other chemical groups into proteins to better understand the molecular basis of protein function.

Education

Ph.D., Macromolecular and Cellular Structure and Chemistry, The Scripps Research Institute, 1996
A.B., Washington University in St. Louis, 1992

Professional Experience

A.B., Chemistry, Washington University, St. Louis, MO, magna cum laude, 1992

Ph.D., The Scripps Research Institute, 1996

Postdoctoral Associate, Caltech, 1997

Assistant Professor, The Scripps Research Institute, 1997 

Awards & Professional Activities

Alfred P. Sloan Fellow 2001-2003; 
Vincent du Vigneaud Award, American Peptide Society, 2010
Max Bergmann Circle Gold Medal: 2011
Editorial Boards,  Bioconjugate Chemistry, Journal of Peptide Science, International Journal of Peptide Research and Therapeutics. 
Council member: American Peptide Society.
 

Selected References

Metanis, N., Keinan, E., Dawson, P.E., Traceless ligation of cysteine peptides using selective deselenization. Angewandte Chemie-International Edition 2010, 49(39), 7049-53.  

Brunel, F.M., Lewis, J.D., Destito, G, Steinmetz, N.F., Manchester, M., Stuhlmann, H., Dawson, P.E., A hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting. Nano Letters 2010, 10(3), 1093-97

Dawson G., Schroeder C., Dawson P.E., Palmitoyl:protein thioesterase (PPT1) inhibitors can act as pharmacological chaperones in infantile Batten disease, Biochem Biophys Res Commun 2010, 395(1), 66-9

Dirksen, A., Yegneswaran, S., Dawson, P.E., Bisaryl hydrazones as exchangeable biocompatible linkers. Angewandte Chemie-International Edition 2010, 49(11), 2023-27

Blanco-Canosa, J.B., Dawson, P.E., An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation. Angewandte Chemie-International Edition 2008, 47(36), 6851-55. 

Links

The Skaggs Institute Scientific Report