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SEMINARIO GERENCIA QUIMICA 2010
"Self-Assembled Peptide Nanostructures: A New Frontier in
Organic Nanotechnology"
Ehud Gazit
Department Molecular Microbiology and Biotechnology, Chair
of Nano-Biology, Tel Aviv University, Tel Aviv 69978, Israel
The formation of ordered amyloid fibrils is the hallmark of
several diseases of unrelated origin. In spite of its grave
clinical consequence, the mechanism of amyloid formation is
not fully understood. We have suggested, based on
experimental and bioinformatic analysis, that aromatic
interactions may provide energetic contribution as well as
order and directionality in the molecular-recognition and
self-association processes that lead to the formation of
these assemblies. This is in line with the well-known
central role of aromatic-stacking interactions in
self-assembly processes.
Our works on the mechanism of aromatic peptide self-assembly,
lead to the discovery that the diphenylalanine recognition
motif of the Alzheimer's beta-amyloid polypeptide
self-assembles into ordered peptide nanotubes with a
remarkable persistence length. Other aromatic homodipeptides
could self-assemble in nano-spheres, nano-plates, nano-fibrils
and hydrogels with nano-scale order. We demonstrated that
the peptide nanostructures have unique chemical, physical
and mechanical properties including ultra-rigidity as
aromatic polyamides. We also demonstrated the ability to use
these peptide nanostructures as casting mold for the
fabrication of metallic nano-wires and coaxial nano-cables.
The application of the nanostructures was demonstrated in
various fields including electrochemical biosensors, tissue
engineering, and molecular imaging.
Finally, we had developed ways for depositing of the peptide
nanostructures and their organization. We had use inkjet
technology as well as vapour deposition methods to coat
surface and from the peptide "nano-forests".
We are currently using this notion, as well as a novel
-breakage strategy that was developed in our laboratory, for
the development of novel inhibitors of the process of
amyloid formation by utilizing hetero-aromatic interactions.
Our lead compound is a novel chemical entity that inhibits
the formation of -amyloid oligomers in vitro and
protects cultured cell and isolated cortical neurons from
cytotoxic effect of -amyloid aggregates. Chronic
administration of the compound was shown safe and
significantly effective in preventing memory impairment in
this animal model as assayed by Morris Water Maze
experiments. Taken together, our hypothesis provides a new
approach to understand the self-assembly mechanism that
governs amyloid formation and indicates possible ways to
control this process.
Relevant publications:
Reches, M, & Gazit, E. (2003) Casting Metal Nanowires Within
Discrete Self-Assembled Peptide Nanotubes. Science 300,
625-627.
Reches, M., & Gazit, E. (2004) Formation of Closed-Cage
Nanostructures by Self-Assembly of Aromatic Dipeptides. Nano
Lett. 4, 581-585.
Yemini, M., Reches, M., Rishpon, J., & Gazit, E. (2005)
Novel Electrochemical Biosensing Platform Using
Self-Assembled Peptide Nanotubes. Nano Lett. 5, 183-186.
Kol, N., Abramovich, L., Barlam, D., Shneck, R. Z., Gazit E.
, & Rousso, I. (2005) Self-Assembled Peptide Nanotubes are
Uniquely Rigid Bioinspired Supramolecular Structures. Nano
Lett. 5, 1343 -1346.
Mahler, A., Reches, M., Rechter, M., Cohen, S., and Gazit,
E. (2006) Novel Self-Assembled Gel Biomaterial Composed of
Modified Aromatic Dipeptide. Adv. Mater. 18, 1365-1370.
Carny, O., Shalev, D., and Gazit, E. (2006) Fabrication of
Coaxial Metal Nanowires Using Self-Assembled Peptide
Nanotube Scaffold. Nano Lett. 6, 1594-1597.
Reches, M., and Gazit, E. (2006) Controlled Patterning of
Aligned Self-Assembled Peptide Nanotubes. Nature
Nanotechnol.1, 195-200.
Adler-Abramovich, L., and Gazit, E. (2008) Controlled
pattering of peptide nanotubes and nanospheres using inkjet
printing technology. J.
Pep. Sci. 14, 217-223.
Gazit, E. (2008) Bioactive nanostructures branch out. Nature
Nanotech. 1,
8-9
Frydman-Marom, A. Rechter, M. Shefler, I., Bram, Y., Shalev,
D. E., and Gazit, E. (2009) Cognitive Performance Recovery
of Alzheimer's Disease Model Mice by Modulating Early
Soluble Amyloidal Assemblies. Angew Chem Int Ed. Engl. 48,
1981-1986.
Adler-Abramovich et al., and Gazit E. (2009) Self-assembled
arrays of peptide nanotubes by vapour deposition. Nature
Nanotech. 4, 849-854.
Ostrov, N. and Gazit, E. (2010) Genetic engineering of
biomolecular scaffolds for the fabrication of organic and
metallic nanowires. Angew.
Chem. Int. Ed. Engl. 49, 3018-3021.
Martes 3 de Agosto - 14 horas
Aula de Nivel 63 - TANDAR
CNEA - Centro Atomico Constituyentes
Av. Gral. Paz 1499 (y Constituyentes)
6772-7065 / 7007 / 7072 / 7081
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