Synthetic polypeptide materials for biomedical applications
Timothy J. Deming
Departments of Bioengineering and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095
The use of low-valent metal complexes for the polymerization of alpha-amino acid-N-carboxyanhydrides (NCAs) will be presented. Using these initiators, we have prepared block copolypeptides containing a variety of both hydrophilic and hydrophobic domains. The hydrophilic chains are composed of either cationic, anionic, or custom non-ionic residues and the hydrophobic chains are composed of natural non-polar amino acid residues such as leucine, valine and phenylalanine. By working with polypeptides, we have used the secondary structures present in the block domains to substantially alter the self-assembly of the polymers in aqueous solution.
Similar to small molecule surfactants and lipids, synthetic block copolymers are able to self-assemble into ordered nanostructures via microphase separation of the polymeric components. We have studied the self-assembly of block copolypeptides as synthetic materials that possess the ability to self-assemble into specifically defined, functional nanostructures. The controlled assembly of block copolypeptides into discrete ordered structures can yield materials valuable for biomedical and nanotechnology applications. Examples would be drug and gene delivery, where the shape of the complexes would favor selective interactions with different biological surfaces, as well as bioactive coatings and hierarchically organized composites. The synthesis, self-assembly, and properties of three classes of amphiphilic block copolypeptide systems will be presented: polypeptide vesicles for gene delivery, double nanoemulsions for therapeutic delivery, and hydrogels for central nervous system therapies.
CV of Timothy J. Deming
EDUCATION:
8/1989 - 10/1993 University of California Berkeley, CA
Ph.D. in Chemistry, Advisor
Ph.D. thesis research with Dr. Bruce M. Novak
Research encompassing polymer synthesis using organometallic catalysis, elucidation of polymerization mechanisms, and physical properties of helical macromolecules.
9/1985 - 6/1989 University of California Irvine, CA
B.S. in Chemistry.
Undergraduate research with Dr. William J. Evans, 6/1987 - 6/1989.
Research activities involved exploration and expansion of the chemistry of cerium(IV) through synthesis of alkoxide and organometallic complexes.
Work Experience
7/06 – Present Chair, Bioengineering Department, UCLA
7/06 – 1/09 Chair, Biomedical Engineering, Interdepartmental Program, UCLA
7/04 – Present Professor, Bioengineering and Chemistry Departments, UCLA
7/03 - 6/04 Professor, Materials and Chemistry Departments, UCSB
7/99 - 6/03 Associate Professor, Materials and Chemistry Departments, UCSB
2/96 - 6/99 Assistant Professor. Materials and Chemistry Departments, UCSB
3/95 - 1/96 Assistant Professor, Materials Department, UCSB
11/93 - 3/95 Postdoctoral research associate with Professor David A. Tirrell
University of Massachusetts, Amherst, MA
Awards and Honors
IUPAC Macromolecular Division Young Scientist Award 2004
MRS Young Investigator Award 2003
Camille Dreyfus Teacher-Scholar 2000
3M Non-Tenured Faculty Award 1999
Beckman Young Investigator Award 1998-2000
Alfred P. Sloan Research Fellow 1998-2000
National Science Foundation CAREER Award 1997-2001
Office of Naval Research Young Investigator Award 1996-1999
University of California, Regents Junior Faculty Fellow 1996
ACS Unilever Award for Outstanding Graduate Research in Polymer Chemistry 1994
NIH National Research Service Award Postdoctoral Fellow 1993 – 199
Selected Publications
1. “Biocompatibility of Amphiphilic Diblock Copolypeptide Hydrogels in the Central Nervous System”. Yang, C.-Y.; Song, B.; Ao, Y.; Nowak, A. P.; Abelowitz, R. B.; Korsak, R. A.; Havton L. A.; Deming, T. J.; Sofroniew, M. V. Biomaterials, 2009, 30, 2881-2898.
2. "Nanoscale Double Emulsions Stabilized by Single Component Block Copolypeptides" Hanson, J.A.; Chang, C.; Graves, S.; Li, Z.; Mason, T.G.; and Deming, T.J. Nature, 2008, 455, 85-88.
3. "Synthetic Polypeptides for Biomedical Applications" Deming, T.J. Progress in Polymer Science, 2007, 32, 858-875.
4. “Polyarginine Segments in Block Copolypeptides Drive Both Vesicular Assembly and Intracellular Delivery” Holowka, E. P.; Sun, V. Z.; Kamei, D. T.; Deming, T. J. Nature Materials, 2007, 6, 52–57.
5. “Polypeptide and Polypeptide Hybrid Copolymer Synthesis via NCA Polymerization” Deming, T. J. Advances in Polymer Science, 2006, 202, 1-18.
6. “Monoliths of Aligned Silica-Polypeptide Hexagonal Platelets” Bellomo, E. G.; Deming, T. J. J. Am. Chem. Soc. , 2006, 128, 2276-2279.
7. “Charged Polypeptide Vesicles with Controllable Diameter” Holowka, E. P.; Pochan, D. J.; Deming, T. J. J. Am. Chem. Soc. , 2005, 127, 12423 - 12428.
8. “Aqueous Cholesteric Liquid Crystals Using Uncharged Rod-Like Polypeptides” Bellomo, E. G.; Davidson, P.; Impéror-Clerc, M.; Deming, T. J. J. Am. Chem. Soc. 2004, 126, 9101-9105.
9. “Rheology of Block Copolypeptide Solutions: Hydrogels with Tunable Properties”. Breedveld, V.; Nowak, A. P.; Sato, J.; Deming, T. J.; Pine, D. J. Macromolecules , 2004, 37, 3943-3953.
10. “Stimuli Responsive Polypeptide Vesicles via Conformation Specific Assembly” Bellomo, E.; Wyrsta, M. D.; Pakstis, L.; Pochan, D. J.; Deming, T. J. Nature Materials, 2004, 3, 244-248.
11. “Rapidly Recovering Hydrogel Scaffolds From Self-Assembling Diblock Copolypeptide Amphiphiles”. Nowak, A. P.; Breedveld, V.; Pakstis, L.; Ozbas, B.; Pine, D. J.; Pochan, D.; Deming, T. J. Nature , 2002, 417, 424-428.
12. “A Parallel Synthetic Approach for the Analysis of Membrane Interactive Copolypeptides”. Wyrsta, M. D.; Cogen, A. L.; Deming, T. J. J. Am. Chem. Soc. , 2001, 123, 12919-12920.
13. “Controlled Polymerization of b-Lactams Using Metal-Amido Complexes. Synthesis of Block Copoly(b-Peptides)”. Cheng, J.; Deming, T. J. J. Am. Chem. Soc., 2001, 123, 9457-9458.
14. "Chain Initiation Efficiency in Cobalt- and Nickel-Mediated Polypeptide Synthesis". Deming, T. J. and Curtin, S. A. J. Am. Chem. Soc. , 2000, 122, 5710-5717.
15. "Biomimetic Synthesis of Ordered Silica Structures Mediated by Block Copolypeptides". Cha, J. N.; Stucky, G. D.; Morse, D. E. and Deming, T. J. Nature , 2000, 403, 289-292.
16. "Methylated Mono- and Diethyleneglycol Functionalized Polylysines: Nonionic, Helical, Water Soluble Polypeptides". Yu, M.; Nowak, A. P.; Pochan, D. P. and Deming, T. J. J. Am. Chem. Soc. , 1999, 121, 12210-12211.
17. "Initiators for End-Group Functionalized Polypeptides via Tandem Addition Reactions". Curtin, S. A. and Deming, T. J. J. Am. Chem. Soc. , 1999, 121, 7427-7428.
18. "Role of L-3,4-Dihydroxyphenylalanine in Mussel Adhesive Proteins". Yu, M.; Hwang, J.; Deming, T. J. J. Am. Chem. Soc. 1999, 121, 5825-5826.
19. "Amino Acid Derived Nickelacycles: Intermediates in Nickel Mediated Polypeptide Synthesis". Deming, T. J. J. Am. Chem. Soc., 1998, 120, 4240-4241.
20. "Facile Synthesis of Block Copolypeptides of Defined Architecture". Deming, T. J. Nature, 1997, 390, 386-389.
21. 25) "Transition Metal-Amine Initiators for Preparation of Well-Defined Poly(gamma-benzyl L-glutamate)". Deming, T. J. J. Am. Chem. Soc., 1997, 119, 2759-2760.
