Dawson, Philip - The Scripps Research Institute

研究领域

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.

近期论文

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Algar, WR, Wegner, D, Huston, AL, Blanco-Canosa, JB, Stewart, MH, Armstrong, A, Dawson, PE, Hildebrandt, N and Medintz, IL. "Quantum dots as simultaneous acceptors and donors in time-gated forster resonance energy transfer relays: characterization and biosensing." J Am Chem Soc 2012 134(3): 1876-1891. Buckhout-White, S, Ancona, M, Oh, E, Deschamps, JR, Stewart, MH, Blanco-Canosa, JB, Dawson, PE, Goldman, ER and Medintz, IL. "Multimodal Characterization of a Linear DNA-Based Nanostructure." ACS Nano 2012. Algar, WR, Prasuhn, DE, Stewart, MH, Jennings, TL, Blanco-Canosa, JB, Dawson, PE and Medintz, IL. "The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry." Bioconjugate Chemistry 2011 22(5): 825-858. Brik, A, Dawson, PE and Kent, SBH. "Chemical Protein Synthesis." Israel Journal of Chemistry 2011 51(8-9): 852-853. Canosa, JBB and Dawson, PE. "Wittig Ligation." Biopolymers 2011 96(4): 438-438. Dawson, PE. "Native Chemical Ligation Combined with Desulfurization and Deselenization: A General Strategy for Chemical Protein Synthesis." Israel Journal of Chemistry 2011 51(8-9): 862-867. Delehanty, JB, Bradburne, CE, Boeneman, K, Blanco-Canosa, JB, Susumu, K, Deschamps, JR, Brunel, FM, Dawson, PE and Medintz, IL. "Achieving cytosolic delivery of quantum dot nanoa*ssemblies: From polymers to peptides." Abstracts of Papers of the American Chemical Society 2011 241. Delehanty, JB, Bradburne, CE, Susumu, K, Boeneman, K, Mei, BC, Farrell, D, Blanco-Canosa, JB, Dawson, PE, Mattoussi, H and Medintz, IL. "Spatiotemporal Multicolor Labeling of Individual Cells Using Peptide-Functionalized Quantum Dots and Mixed Delivery Techniques." Journal of the American Chemical Society 2011 133(27): 10482-10489. Ingale, S and Dawson, PE. "On Resin Side-Chain Cyclization of Complex Peptides Using CuAAC." Organic Letters 2011 13(11): 2822-2825. Morgner, F, Stufler, S, Geissler, D, Medintz, IL, Algar, WR, Susumu, K, Stewart, MH, Blanco-Canosa, JB, Dawson, PE and Hildebrandt, N. "Terbium to Quantum Dot FRET Bioconjugates for Clinical Diagnostics: Influence of Human Plasma on Optical and A*ssembly Properties." Sensors 2011 11(10): 9667-9684. Oh, E, Delehanty, JB, Sapsford, KE, Susumu, K, Goswami, R, Blanco-Canosa, JB, Dawson, PE, Granek, J, Shoff, M, Zhang, Q, Goering, PL, Huston, A and Medintz, IL. "Cellular Uptake and Fate of PEGylated Gold Nanoparticles Is Dependent on Both Cell-Penetration Peptides and Particle Size." Acs Nano 2011 5(8): 6434-6448. Sapsford, KE, Granek, J, Deschamps, JR, Boeneman, K, Blanco-Canosa, JB, Dawson, PE, Susumu, K, Stewart, MH and Medintz, IL. "Monitoring Botulinum Neurotoxin A Activity with Peptide-Functionalized Quantum Dot Resonance Energy Transfer Sensors." Acs Nano 2011 5(4): 2687-2699. Susumu, K, Oh, E, Delehanty, JB, Blanco-Canosa, JB, Johnson, BJ, Jain, V, Hervey, WJ, Algar, WR, Boeneman, K, Dawson, PE and Medintz, IL. "Multifunctional Compact Zwitterionic Ligands for Preparing Robust Biocompatible Semiconductor Quantum Dots and Gold Nanoparticles." Journal of the American Chemical Society 2011 133(24): 9480-9496. Venter, PA, Dirksen, A, Thomas, D, Manchester, M, Dawson, PE and Schneemann, A. "Multivalent Display of Proteins on Viral Nanoparticles Using Molecular Recognition and Chemical Ligation Strategies." Biomacromolecules 2011 12(6): 2293-2301. Zimmermann, J, Thielges, MC, Seo, YJ, Dawson, PE and Romesberg, FE. "Cyano Groups as Probes of Protein Microenvironments and Dynamics." Angewandte Chemie-International Edition 2011 50(36): 8333-8337. Zimmermann, J, Thielges, MC, Yu, W, Dawson, PE and Romesberg, FE. "Carbon-Deuterium Bonds as Site-Specific and Nonperturbative Probes for Time-Resolved Studies of Protein Dynamics and Folding." Journal of Physical Chemistry Letters 2011 2(5): 412-416. Tiefenbrunn, T.K., Dawson, P.E. Chemoselective Ligation Techniques: Modern Applications of Time-Honored Chemistry. Biopolymers 2010 94, 95-106. Shekhter, T., Metanis, N., Dawson, P.E., Keinan, E. A residue outside the active site CXXC motif regulates the catalytic efficiency of Glutaredoxin 3. Molecular Biosystems 2010 6, 241-248. Sapsford, K.E., Blanco-Canosa, J.B., Dawson, P.E., Medintz, I.L. Detection of HIV-1 Specific Monoclonal Antibodies Using Enhancement of Dye-Labeled Antigenic Peptides. Bioconjugate Chemistry 2010 21, 393-398. Prasuhn, D.E., Deschamps, J.R., Susumu, K., et al. Polyvalent Display and Packing of Peptides and Proteins on Semiconductor Quantum Dots: Predicted Versus Experimental Results. Small 2010 6, 555-564.