PeptoidsPhysics 43 Santa Rosa Junior CollegeSpring Semester 2011

Researchers:Daniel Janiak

By request: a photo of me (at the nanotech forum)

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Ronald Zuckermann, Ph.D

“We’re using nature as our guide to develop functional, stable nanostructures.”

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

http://www.daviddarling.info/images/tryptophan.jpg

Tryptophan – the largest amino acid with a length of approximately 1.2 nm. Peptoid monomers are comparable in size.

Peptoids vs Peptides

• The folding of such chains in a solvent spontaneously creates complex, functional structures.

Peptoid Peptide

http://metamodern.com/2008/12/01/peptoids-at-the-molecular-foundry/

http://www.chem.purdue.edu/courses/chm333/hemoglobin.JPG

/ http://www.goldbamboo.com/images/content/5530-hemoglobin-t-r-state-ani-hemoglobin.gif

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.

Plastics simple, useful polymers

Polyvinylidene chloride (cling wrap)

PolyethylenePolystyrene

?DurabilityEase of manufactureBroad application (flexibility)Variety of physical properties.(many more!)

Achieve complicated physiological tasksSelf-assemblyChemical catalysisBinding of other molecules with high specificity(many more!)

SignatureStructures

Alpha-helix (2008*)Magainin-2 in DPPC micelles

[Protein Data Bank (PDB) ID Code 2MAG].

©2008 by National Academy of Sciences

Chongsiriwatana N P et al. PNAS 2008;105:2794-2799

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

Sheets are more difficult to create because both inter- and intra-chain interactions must be considered.

With the right construction, however, sheets self-assemble.

http://byrkeley.blogspot.com/2010_06_01_archive.html

Peptoid sheets

http://www.nature.com/nmat/journal/v9/n5/fig_tab/nmat2742_F3.html

Magnified:

Aberration-corrected TEM of Peptoid Chains

(*4.5 angstrom = 0.45 nanometers)

http://www.lbl.gov/publicinfo/newscenter/features/2008/MSD-nano-jaws.html

“Nanojaws”(2008)

Not just shape mimicry, but natural protein function mimicry as well.

Additionally, a synthetic peptoid version is more durable → not limited to a narrow range of temperatures and pH levels.

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A bound molecule of zinc(Recall: Hemoglobin binds Fe)

How are these structures created / synthesized?

http://upload.wikimedia.org/wikipedia/commons/3/3e/Peptoid_struc_synth.png

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.

An Example of an Actual peptoid “building

Chirayil S et al. Nucl. Acids Res. 2009;37:5486-5497

© 2009 The Author(s)

Kit.”

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Another Example, this one from the Molecular Foundary in Berkeley, CA.

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Examples of Current Research

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC89291/http://www.thesahara.info/mrsa/staph-bio.jpg

New AntibioticsChiron 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://topnews.ae/images/alzheimers.jpghttp://www.scientificamerican.com/article.cfm?id=alzheimers-blood-test

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://newscenter.lbl.gov/wp-content/uploads/nanorope.jpg

Nanorope(at Lawrence Berkeley National Laboratory, 2011)

Self-assembling!Atom-by-atom makeup can be chosenHelices 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

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As Richard Feynman put it ….

There’s plenty of room at the bottom.