Tel Aviv University (TAU)- Research Group
Prof. Ehud Gazit
Chief Scientist of the Ministry of Science and Technology
Vice president of research and development and the chairman of Ramot,
the technology office of TAU.
Department of Molecular Microbiology and Biotechnology
The George S. Wise Faculty of Life Sciences
Tel Aviv University
Prof. Ehud Gazit
Building: Green, Molecular Microbiology and Biotechnology Department
Office phone: 972-3-640-9030
Lab phone: 972-3-6407498/5451
Office fax: 972-3-6407499/9407
Home page: http://www.tau.ac.il/lifesci/departments/biotech/members/gazit/gazit.html
Self-Assembly of Short Aromatic Peptides: from Amyloid Disease to Nanotechnology
The research is directed toward the study of protein folding, misfolding, and peptide self-assembly. The work has resulted in the identification of elements that facilitate the assembly of amyloid fibrils, associated with Alzheimer's disease, and novel ways to inhibit this process was identified. The Prof. Gazit's laboratory was the first to discover aromatic dipeptides that form variety of tubular and spherical nanostructures with unique mechanical and chemical properties. Applications of these nano-assemblies include ultra-sensitive biosensors, energy-storage devices, metallic nanowires and nano-bio-engineering. These properties of the peptide nanostructures, taken together with their biological compatibility and remarkable mechanical and chemical stability, may provide very important tools for future biomedical applications.
Nano-carrier based on peptide nanostructures for controlled drug delivery
Three complementary nano-carrier approaches will be used to provide a coherent platform based of diphenylalanine-derived peptides with both surface active and encapsulating ability:
- Peptide tubular nanocarriers
- Peptide spherical nanocarriers
- Peptide based hydrogel nanocarriers
(A) Transmitting electron microscope micrograph of magnetide-coated peptide nanotube (scale bar 100 nm). (B) Schematic presentation of magnetide-coated peptide nanotube. (C) Scanning electron microscope micrograph of magnetide-coated peptide nanotube (scale bar 200 nm). (D) E-SEM micrograph of magnetite-loaded nanosphere (scale bar 200 nm). (E) Fluorescence microscope image of the fluorescence-labeled nanospheres. (F) The typical nanosphere decorated with gold particles (scale bar 100 nm). (G) Transmitting electron microscope micrograph of peptide nanosphere of average radius 100 nm. (H) Transmitting electron microscope micrograph shows that the size of the NPs is between 44-80 nm and not around 100 nm. (I) Transmitting electron microscope micrograph image of gold nanoparticles encapsulated by hydrogel NPs (scale bar 300 nm). (J) Schematic presentation of hydrogel nanoparticles dispersed in oil. (K) Florescent microscopy image of hydrogel NPs encapsulating P21 RE53 double stranded DNA molecule containing fluorescein.
All three types of diphenylalanine-derived nanocarriers have approved ability to be both decorated or/and filled with therapeutic and imaging agents and applied for following drug delivery applications:
- Recognition - The nanocarriers will be decorated with biological recognition modules such as the antibodies developed by the consortium (Benhar’s group), cell targeting ligands (CTL) to active targeting the nanoparticles to selected tumors and combining activatable cell penetrating peptide (aCPP) (David’s group).
- Diagnostic and imaging applications - Encapsulation of inorganic materials such as ferrous oxide or gadolinium for MRI and quantum dots or organic dyes for optical imaging.
- Therapeutic - Incorporation of microRNA (miRs) and (small interfering RNA (siRNA) (Satchi-Fainaro’s group) and the other partners (Peer, Michaeli) into the peptide nanocarriers.
Scherzer-Attali R., Shaltiel-Karyo R., Adalist YH., Segal D., Gazit E. (2012) Generic inhibition of amyloidogenic proteins by two naphthoquinone-tryptophan hybrid molecules. Proteins. 80, 8, 1962-1973.
Adler-Abramovich L., Vaks L., Carny O., Trudler D., Magno A., Caflisch A., Frenkel D., Gazit E. (2012). Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria. Nat Chem Biol. 10, 1038.
Amdursky N., Koren I., Gazit E., Rosenman G. Adjustable photoluminescence of peptide nanotubes coatings. (2011) J Nanosci Nanotechnol. 11(10), 9282-9286.
Frydman-Marom A., Convertino M., Pellarin R., Lampel A., Shaltiel-Karyo R., Segal D., Caflisch A., Shalev D.E., Gazit E. (2011) Structural basis for inhibiting β-amyloid oligomerization by a non-coded β -breaker-substituted endomorphin analogue. ACS Chem Biol. 6(11), 1265-1276.
Frydman-Marom A., Shaltiel-Karyo R., Moshe S., Gazit E. (2011) The generic amyloid formation inhibition effect of a designed small aromatic β-breaking peptide. Amyloid. 18(3), 119-127.
Even N., Adler-Abramovich L., Buzhansky L., Dodiuk H., Gazit E. (2011)
Improvement of the mechanical properties of epoxy by peptide nanotube fillers. Small. 7(8), 1007-1011.
Andreotti G., Vitale R.M., Avidan-Shpalter C., Amodeo P., Gazit E., Motta A. (2011) Converting the highly amyloidogenic human calcitonin into a powerful fibril inhibitor by three-dimensional structure homology with a non-amyloidogenic analogue. J Biol Chem. 2011 286(4), 2707-2718.
Carny O., Gazit E. (2011) Creating prebiotic sanctuary: self-assembling supramolecular Peptide structures bind and stabilize RNA. Orig Life Evol Biosph. 41(2), 121-132.
Gazit E. Bioinspired chemistry: Diversity for self-assembly. (2010) Nat Chem. 2(12), 1010-1011.
Shaltiel-Karyo R., Frenkel-Pinter M., Egoz-Matia N., Frydman-Marom A., Shalev D.E., Segal D., Gazit E.(2010) Inhibiting α-synuclein oligomerization by stable cell-penetrating β-synuclein fragments recovers phenotype of Parkinson's disease model flies. PLoS One. 5(11), 13863.
Adler-Abramovich L., Aronov D., Beker P., Yevnin M., Stempler S., Buzhansky L., Rosenman G., Gazit E. (2009) Self-assembled arrays of peptide nanotubes by vapour deposition. Nat Nanotechnol. 4(12), 849-854.
Levy-Sakin M., Shreberk M., Daniel Y., Gazit E. (2009) Targeting insulin amyloid assembly by small aromatic molecules: toward rational design of aggregation inhibitors. Islets. 1(3), 210-215.
Orbach R., Adler-Abramovich L., Zigerson S., Mironi-Harpaz I., Seliktar D., Gazit E. (2009) Self-assembled Fmoc-peptides as a platform for the formation of nanostructures and hydrogels. Biomacromolecules. 10(9), 2646-2651.
Gazit E. (2008) Molecular self-assembly: bioactive nanostructures branch out. Nat Nanotechnol. 3(1), 8-9.
Reches M., Gazit E. (2006) Controlled patterning of aligned self-assembled peptide nanotubes. Nat Nanotechnol. 1(3), 195-200.
Kol, N., Abramovich, L., Barlam, D., Shneck, R. Z., Gazit E. , & Rousso, I. (2005) Self-Assembled Peptide Nanotubes Exhibit Unique Mechanica Stiffness. Nano Lett. 5, 1343 -1346.
Yemini, M., Reches, M., Rishpon, J., & Gazit, E. (2005) Novel Electrochemical Biosensing Platform Using Self-Assembled Peptide Nanotubes. Nano Lett. 5, 183-186.
Reches, M., & Gazit, E. (2004) Formation of Closed-Cage Nanostructures by Self-Assembly of Aromatic Dipeptides. Nano Lett. 4, 581-585.
Reches, M., & Gazit, E. (2003) Casting Metal Nanowires within Discrete Self-Assembled Peptide Nanotubes. Science 300, 625-627.
Tel Aviv University (TAU)
- Dan Peer
- Ronit Satchi-fainaro
- Ehud Gazit
- Rimona Margalit
- Itai Benhar
- Doron Shabat
- Moshe Portnoy
- Vered Padler-Karavani
Ben-Gurion University of the Negev (BGU)
The Hebrew University of Jerusalem (HUJI)
Bar-Ilan University (BIU)