Peptoids
Physics 43
Santa Rosa Junior College
Spring Semester 2011
Researchers:
Daniel Janiak
By request: a
photo of me (at
the nanotech
forum)
“We’re using nature as our guide
to develop functional, stable
nanostructures.”
Ronald Zuckermann,
Ph.D
?
What are
peptoids?
Bio-inspired nanoparticle polymers (a
description).
By mimicking natural proteins, these
molecules hold the promise of achieving a
bottom-up approach, and self-assembly.
Technical Definition

N-substituted glycine
heteropolymers
Example
(an octamer):
Peptoids are Nanotechnology
Tryptophan – the largest amino acid with a
length of approximately 1.2 nm. Peptoid
monomers are comparable in size.
http://www.daviddarling.info/images/trypt
ophan.jpg
Peptoids vs Peptides
Peptoid
Peptide
• The folding of such chains in a solvent
spontaneously creates complex, functional
structures.
http://metamodern.com/2008/12/01/pept
oids-at-the-molecular-foundry/
An Illustration of Protein Structure:
Hemoglobin
Four separate chains are
organized together, making
a “dimer of dimers.”
Motifs, such as the many alpha helices seen
above are characteristic of secondary
structure, their arrangement with other
motifs is tertiary structure.
http://www.chem.purdue.edu/courses/ch
m333/hemoglobin.JPG /
http://www.goldbamboo.com/images/cont
ent/5530-hemoglobin-t-r-state-ani-
Plastics
simple, useful polymers
Polyvinylidene
chloride
(cling wrap)
Polyethylene
Polystyrene
Achieve complicated
physiological tasks
Self-assembly
Chemical catalysis
Binding of other
molecules with high
specificity
(many more!)
?
Durability
Ease of manufacture
Broad application
(flexibility)
Variety of physical
properties.
(many more!)
Signature
Structures
Alpha-helix (2008*)
Magainin-2 in DPPC micelles
[Protein Data Bank (PDB) ID Code 2MAG].
The helical shape
is a consequence of
the “handedness”
of the individual
monomers.
The result is a
structure that is
more resilient than
one held together
by hydrogen bonds.
*The first ever
helical peptoid was
made in 1997
©2008 by National Academy of Sciences
Chongsiriwatana N P et al. PNAS
2008;105:2794-2799
Peptoid sheets
Sheets are more
difficult to create
because both interand intra-chain
interactions must be
considered.
With the right
construction,
however, sheets selfassemble.
http://byrkeley.blogspot.com/2010_06_01
_archive.html
Aberrationcorrected TEM of
Peptoid Chains
Magnified:
(*4.5 angstrom = 0.45
nanometers)
http://www.nature.com/nmat/journal/v9/n
5/fig_tab/nmat2742_F3.html
“Nanojaws”
(2008)
Not just shape mimicry, but
natural protein function mimicry
as well.
A bound molecule of zinc
(Recall: Hemoglobin binds
Fe)
Additionally, a synthetic
peptoid version is more durable
→ not limited to a narrow range
of temperatures and pH levels.
.
http://www.lbl.gov/publicinfo/newscenter/
features/2008/MSD-nano-jaws.html
How are these
structures created /
synthesized?
A sub-monomer approach
Peptoid monomers can be individually designed and
added one-by-one.
Allows for much freedom in achieving a desired end
structure.
An ideal application for combinatorial chemistry, enabling
rational design and quick screening.
http://upload.wikimedia.org/wikipedia/co
mmons/3/3e/Peptoid_struc_synth.png
An Example of an Actual peptoid “building
Kit.”
Chirayil S et al. Nucl. Acids Res. 2009;37:5486-5497
© 2009 The Author(s)
Another Example, this one from the Molecular
Foundary in Berkeley, CA.
.
Examples of
Current Research
?
New Antibiotics
Chiron Corporation, Emeryville, California (1999)
A peptoid termed “CHIR29498
“and others similar to it were
affective against a wide spectrum
of bacteria, including some
antibiotic-resistant strains.
The required concentrations
were practical: 3 to 12 μg/ml
http://www.ncbi.nlm.nih.gov/pmc/articles/
PMC89291/
http://www.thesahara.info/mrsa/staph-
A New Diagnosis for
Alzheimer's
(2011)
(Thomas Kodadek, of Scripps
Research Institute ,Jupiter,
Florida)
Currently, the disease can
only be definitively diagnosed
by examining brain plaques .
Kodadek’s group identified 3 antibody-binding peptoids which
could identify patients who have the disease with 93% accuracy,
requiring only a simple blood test.
http://topnews.ae/images/alzheimers.jpg
http://www.scientificamerican.com/article.
cfm?id=alzheimers-blood-test
Nanorope
(at Lawrence Berkeley National Laboratory, 2011)
Self-assembling!
Atom-by-atom makeup can be
chosen
Helices can be engineered to have
desired lengths and sequences
Possible Uses:
•Scaffolding for nanoscale
construction
•Drug delivery
•Molecular sensors
•Sieve-like devices
Diameter of above example = 600nm
http://newscenter.lbl.gov/wpcontent/uploads/nanorope.jpg
As Richard Feynman put it ….
There’s plenty of
room at the bottom.
?