Research interests
I am interested in mimicking the way Nature builds
precise 3-dimensional architectures. Can we build artificial
proteins by linking non-natural building blocks into specific sequences
that spontaneously fold into defined tertiary structures? Can we
make huge numbers of sequence variations and select for sequences
that have a desired structure or function? We have developed a
versatile and efficient method of synthesizing biomimetic peptoid
oligomers, as well as robotic combinatorial synthesis tools to
address these questions.
Current projects
- Novel nano-scale architectures based
on the self-assembly of bio-inspired oligomers.
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. The oligomers can fold up into
helices, and the helices can be designed to self-assemble into
compact folded single-chain structures. We plan to explore the
folding and self-assembly of peptoids coupled with new combinatorial
synthesis and screening technologies to discover new nano-structured
materials.
- Combinatorial discovery technologies.
We aim to develop tools to allow the synthesis and screening of
very large (>105 compounds) combinatorial libraries of peptoid
oligomers. We are developing novel solid supports and synthesis
formats to facilitate the high-throughput screening of these
libraries for novel structure and function.
- 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.
Selected publications:
- Utku, Y.; Dehan, E.; Ouerfelli, O.; Piano, F.;
Zuckermann, R.N.; Pagano, M.; Kirshenbaum, K., A peptidomimetic
siRNA transfection reagent for highly effective gene silencing. Mol.
BioSyst. 2006, 2, 312-317.
- Paulick, M.G.; Hart, K.M.; Brinner, K.M.; Tjandra,
M.; Charych, D.H.; Zuckermann, R.N., A Cleavable Hydrophilic Linker
for One-Bead-One-Compound Sequencing of Oligomer Libraries by Tandem
Mass Spectrometry. J. Comb. Chem. 2006, 8,
417-426.
- Huang, K.; Wu, C.W.; Sanborn, T.J.; Patch, J.A.;
Kirshenbaum, K.; Zuckermann, R.N.; Barron, A.E.; Radhakrishnan,
I., A Threaded Loop Conformation Adopted by a Family of Peptoid
Nonamers. J. Am. Chem. Soc. 2006, 128,
1733-1738.
- Lee, B.-C.; Zuckermann, R.N.; Dill, K.A., Folding
a Nonbiological Polymer into a Compact Multihelical Structure. J.
Am. Chem. Soc. 2005, 127, 10999-11009.
- Horn, T.; Lee, B.-C.; Dill, K.A.; Zuckermann,
R.N., Incorporation of Chemoselective Functionalities into Peptoids
via Solid-Phase Submonomer Synthesis. Bioconj. Chem. 2004, 15,
428-435.
- Burkoth, T.S.; Fafarman, A.T.; Charych, D.H.;
Connolly, M.D.; Zuckermann, R.N., Incorporation of Unprotected
Heterocyclic Side Chains into Peptoid Oligomers via Solid-Phase
Submonomer Synthesis. J. Am. Chem. Soc. 2003, 125,
8841-8845.
- Burkoth, T.S.; Beausoleil, E.; Kaur, S.; Tang,
D.; Cohen, F.E.; Zuckermann, R.N., Toward the Synthesis of Artificial
Proteins: The Discovery of an Amphiphilic Helical Peptoid Assembly. Chemistry & Biology 2002, 9,
647-654.
- Nguyen, J.T.; Porter, M.; Amoui, M.; Miller, T.W.;
Zuckermann, R.N.; Lim, W.A., Improving SH3 Domain Ligand Selectivity
Using a Non-natural Scaffold. Chem. Biol. 2000, 7,
463-473.
- Kirshenbaum, K.; Barron, A.E.; Goldsmith, R.A.;
Armand, P.; Bradley, E.K.; Truong, K.T.V.; Dill, K.A.; Cohen,
F.E.; Zuckermann, R.N., Sequence-Specific Polypeptoids: A
Diverse Family of Heteropolymers with Stable Secondary Structure. Proc.
Natl. Acad. Sci. U. S. A. 1998, 95,
4303-4308.
- Huang, C.-Y.; Uno, T.; Murphy, J.E.; Lee, S.;
Hamer, J.D.; Escobedo, J.A.; Cohen, F.E.; Radhakrishnan, R.; Dwarki,
V.; Zuckermann, R.N., Lipitoids - novel cationic lipids for cellular
delivery of plasmid DNA in vitro. Chem. Biol. 1998, 5,
345-354.
- Figliozzi, G.M.; Goldsmith, R.; Ng, S.; Banville,
S.C.; Zuckermann, R.N., Synthesis of N-(substituted)glycine Peptoid
Libraries. Methods Enzymol. 1996, 267,
437-447.
- Zuckermann, R.N.; Martin, E.J.; Spellmeyer, D.C.;
Stauber, G.B.; Shoemaker, K.R.; Kerr, J.M.; Figliozzi, G.M.; Goff,
D.A.; Siani, M.A.; Simon, R.J.; Banville, S.C.; Brown, E.G.; Wang,
L.; Richter, L.S.; Moos, W.H., Discovery of Nanomolar Ligands for
7-Transmembrane G-Protein Coupled Receptors from a Diverse (N-Substituted)Glycine
Peptoid Library. J. Med. Chem. 1994, 37,
2678-2685.
- Zuckermann, R.N.; Kerr, J.M.; Kent, S.B.H.; Moos,
W.H., Efficient Method for the Preparation of Peptoids [Oligo(N-substituted
glycines)] by Submonomer Solid Phase Synthesis. J. Am. Chem.
Soc. 1992, 114, 10646-10647.
Education
Ph.D. Chemistry 1989, University of California,
Berkeley, CA; Thesis Advisor: Prof. Peter Schultz; "Design
and synthesis of hybrid sequence-specific ribonucleases”.
B.S. Chemistry 1984, Harvey Mudd College, Claremont, CA
Past professional positions
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.
Links
Ron’s website: http://www.ronznet.com
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