Facility Director, Biological Nanostructures
User Program Senior Advisor
Ph.D. Chemistry, UC Berkeley, 1989. Advisor: Prof. Peter Schultz
B.S. Chemistry, Harvey Mudd College, 1984
2003 – 2005 Research Fellow, Chiron Corp.
1996 – 2003 Director of Bioorganic Chemistry, Chiron Corp.
1993 – 1996 Associate Director, Bioorganic Chemistry, Chiron Corp.
1991 – 1993 Sr. Scientist, Bioorganic Chemistry, Chiron Corp. Emeryville, CA.
1989 – 1991 Res. Scientist, New Technologies, Protos Corp. Emeryville, CA.
1984 (summer) DuPont Central Research, Wilmington, DE.
1983 (summer) Brookhaven National Lab, Upton, NY.
I am fascinated by the way nature builds precise 3-dimensional nanostructures from the folding of linear polymers. We aim to adapt the fundamental principles of protein folding to man-made polymers, to create novel and robust nanoarchitectures that are capable of specific molecular recognition and catalysis. We have developed a new class of bio-inspired polymer called 'peptoids' that can be synthesized with remarkable efficiency and sequence-specific precision. This enables us to prepare vast combinatorial libraries of information-rich polymers, and screen them for a variety of functions. In close collaboration with theorists, we are discovering the design rules that govern the synthesis of atomically-ordered, protein-mimetic materials to solve frontier problems in energy and materials science.
Peptoids are novel class of sequence-specific oligomer based on an N-substituted glycine backbone. Hundreds of different side-chains can be easily incorporated, and oligomers of up to 50 residues can be efficiently synthesized. These oligomers can fold up into helices, and the helices can further self-assemble into compact folded single-chain structures. We explore the folding and self-assembly of peptoids coupled with new combinatorial synthesis and screening technologies to discover new nano-structured materials.
Free floating ultra-thin two-dimensional crystals from sequence-specific peptoid polymers
The design and synthesis of protein-like polymers is a fundamental challenge in materials science. A biomimetic approach is to explore the impact of monomer sequence on non-natural polymer structure and function. We present the aqueous self-assembly of two peptoid polymers into extremely thin two-dimensional crystalline sheets directed by periodic amphiphilicity, electrostatic recognition, and aromatic interactions. Read the full research paper [access required].
Biomimetic Nanostructures: Creating a High-Affinity Zinc-Binding Site in a Folded Nonbiological Polymer
Sequence-specific heteropolymers are growing in importance as useful tools in chemical biology, drug discovery, delivery, and materials science. Recent advances in synthetic chemistry have made it possible to generate many different types of nonnatural sequence-specific heteropolymers, providing a test of folding principles as well as potential therapeutic and diagnostic materials. Ultimately, we aim to create stable nanostructures with protein-like functions from nonnatural polymers. Read the full research paper.
We develop tools to allow the synthesis and screening of very large (>105 compounds) combinatorial libraries of peptide and peptoid oligomers. We are developing novel solid supports, synthesis formats, screening methods and sequencing techniques to facilitate the high-throughput screening of these libraries for novel structure and function.
High-Throughput Sequencing of Peptoids and Peptide−Peptoid Hybrids by Partial Edman Degradation and Mass Spectrometry
Oligomers of N-substituted glycines, or "peptoids", are a new class of unnatural materials that are capable of mimicking the structure and function of peptides and proteins. A diverse array of biologically active peptoids have been discovered, including carriers for nucleic acid delivery, antimicrobials, lung surfactant mimetics, inhibitors of G-protein-coupled receptors, and ligands of both intracellular and cell surface proteins. Peptoids offer several advantages over peptides as therapeutic or diagnostic agents. Read the full research paper.
Molecular recognition elements for sensor devices
Many new MEMS and NEMS sensors can be fabricated with exceptional sensitivity to detect the binding of analyte molecules. However, a critical element missing from many of these sensors are molecular recognition elements that can selectively bind particular analytes of interest. Most current sensors rely on fairly non-specific interactions like bulk poymer membranes. We aim to screen combinatorial libraries of peptoid oligomers to identify a panel of highly-specific recognition elements.
An interview with Ron Zuckermann about his work
Research press: A Tailorable Nanotube, Formed by a Ring-shaped Protein
Research press: Nanosized Jaws Perform Like Proteins