Directory | Contact | Careers | Intranet | Home

Scripps Research Joint Appointments

Department of Cell 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

Awards & Professional Activities

Vincent du Vigneaud Award 2010; Alfred P. Sloan Fellow 2001-2003; Editorial Board, Letters in Peptide Science 2000-2003; Faculty of 1000, Chemical Biology Section 2001 to present.

Selected References

Hackeng, T.M., Griffin, J.M. and Dawson, P.E. Protein synthesis by native chemical ligation: Expanded scope by straightforward methodology. Proc. Natl. Acad. Sci. USA 96:10068-10073, 1999.

Beligere, G.S. and Dawson, P.E. Design, synthesis, and characterization of 4-ester C12, a model for backbone hydrogen bonding in protein a-Helices. J. Am. Chem. Soc. 122:12079-12082, 2000

Yan, L. and Dawson, P.E. Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization. J. Am. Chem. Soc. 123:526-533, 2001.

Offer, J., Boddy, C.N., Dawson, P.E. Extending synthetic access to proteins with a removable acyl-transfer auxiliary. J. Am. Chem. Soc., in press.

Links

The Skaggs Institute Scientific Report