Scripps Research Joint Appointments

Department of Cell and Molecular Biology
Faculty, Graduate Program

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, California Institute of Technology, 1997
Assistant Professor, The Scripps Research Institute, 1997-present

Awards & Professional Activities

•Alfred P. Sloan Fellow, 1999-2001
•Vincent du Vigneaud Award, 2010
•Gold Medal of the Max Bergmann Kreis, 2011
•Chairman, American Peptide Symposium, 2011
•Co-Chairman, Gordon Research Conference, 2016
•Elected President, American Peptide Society, 2013-2018
•Leonidas Zervas Award, 2014

•100 Invited lectures
•3 Scientific Advisory Boards
•3 Journal Editorial Boards
•>100 Peer Reviewed Publications
•>1,800 citations (ISI) for publication on Native Chemical Ligation
•>35 graduate and postdoctoral students

Selected References

Aldeek F, Hawkins D, Palomo V, Safi M, Palui G, Dawson PE, Alabugin I, Mattoussi H. UV and Sunlight Driven Photoligation of Quantum Dots: Understanding the Photochemical Transformation of the Ligands. Journal of the American Chemical Society. 2015;137(7):2704-14. doi: 10.1021/ja512802x.

Agarwal R, Domowicz MS, Schwartz NB, Henry J, Medintz I, Delehanty JB, Stewart MH, Susumu K, Huston AL, Deschamps JR, Dawson PE, Palomo V, Dawson G. Delivery and Tracking of Quantum Dot Peptide Bioconjugates in an Intact Developing Avian Brain. ACS chemical neuroscience. 2015. doi: 10.1021/acschemneuro.5b00022.

Adhikary R, Zimmermann J, Dawson PE, Romesberg FE. IR probes of protein microenvironments: utility and potential for perturbation. Chemphyschem : a European journal of chemical physics and physical chemistry. 2014;15(5):849-53. doi: 10.1002/cphc.201400017.

Adhikary R, Zimmermann J, Liu J, Forrest RP, Janicki TD, Dawson PE, Corcelli SA, Romesberg FE. Evidence of an unusual N-H...N hydrogen bond in proteins. Journal of the American Chemical Society. 2014;136(39):13474-7. doi: 10.1021/ja503107h.

Lamberto I, Lechtenberg BC, Olson EJ, Mace PD, Dawson PE, Riedl SJ, Pasquale EB. Development and Structural Analysis of a Nanomolar Cyclic Peptide Antagonist for the EphA4 Receptor. ACS chemical biology. 2014. doi: 10.1021/cb500677x.

Scott AM, Algar WR, Stewart MH, Trammell SA, Blanco-Canosa JB, Dawson PE, Deschamps JR, Goswami R, Oh E, Huston AL, Medintz IL. Probing the Quenching of Quantum Dot Photoluminescence by Peptide-Labeled Ruthenium(II) Complexes. The journal of physical chemistry C, Nanomaterials and interfaces. 2014;118(17):9239-50. doi: 10.1021/jp501039w.

Thompson DA, Evans EG, Kasza T, Millhauser GL, Dawson PE. Adapter reagents for protein site specific dye labeling. Biopolymers. 2014;102(3):273-9. doi: 10.1002/bip.22481.

Wendeler M, Grinberg L, Wang X, Dawson PE, Baca M. Enhanced catalysis of oxime-based bioconjugations by substituted anilines. Bioconjugate chemistry. 2014;25(1):93-101. doi: 10.1021/bc400380f.

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