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Molecular Structure and Self-Assembly at the Nano-Scale

The central dogma in the study of protein folding suggests that the thermodynamically-favorable state of proteins under physiological conditions is their folded one. However, there are number of cases in which the favorable states of proteins are rather unfolded, partially folded (e.g., “molten globular”), or misfolded (e.g., nonspecific aggregates or amyloid fibrils). These observations lead to much interest in the significance and mechanism of formation of such unfolded, misfolded or partially folded structures in physiological as well as pathological conditions.

 In our lab we utilize a variety of biochemical, biophysical and molecular biology methodologies to study the mechanism and significance of protein unfolding and misfolding. The experimental systems used are diverse and the partial list includes several bacterial toxin-antidote systems, type II diabetes-related amyloidogenic proteins and peptides, and the VHL tumor suppressor protein. We also study the mechanism of non-specific aggregation of generic unrelated proteins. Another line of research is directed toward the elucidation of the mechanism of action of chemical chaperons and their effect on folding, aggregation and amyloid formation.

Amyloid formation and degenerative disease

The formation of well-ordered amyloid fibrils is the hallmark of several diseases of unrelated origin. A partial list includes Alzheimer’s disease, Type II diabetes, and prion disease such as bovine spongiform encephalopathy (BSE) and Creutzfeldt Jakob Disease (CJD). In spite of its grave clinical consequence, the mechanism of amyloid fibrils formation is not fully understood. We suggest, based on experimental and bioinformatical analysis, that aromatic stacking interactions may provide energetic contribution as well as order and directionality in the self-assembly of ordered amyloid structures. Indeed, using rational probing and systematic peptide array screens we had identify several novel and very short (as short as tetrapeptide) amyloidogenic motifs that include aromatic moieties. This is in line with the well-known central role of aromatic stacking interactions in self-assembly of many supramolecular structures. Therefore, it appears that the molecular recognition and self-assembly process that lead to the formation of order structures is being mediated by small structural elements. In the path of our reductionist approach toward the identification of the shortest motifs that mediate the self-assembly of the fibrils, we demonstrated that the diphenylalanine core-recognition motif of the Alzheimer’s beta-amyloid polypeptide contains all the molecular information needed for efficient self-assembly into well-ordered, stiff, and elongated nanotubes. We also revealed the important of early intermediates that are small in size and transient in the membrane permeating activity of amyloidogenic proteins. Therefore, the inhibition of the very early step of recognition appears to be crucial. To address this issue, we had developed novel inhibition methodologies that are based on hetero-aromatic interaction using small-molecule and peptide-derived compounds. We also demonstrated the potent inhibitory activity of non-natural beta-breakers such as the alpha-aminoisobutyric acid.

Nano-scale Peptide Assemblies

Following our mechanistic studies on amyloid fibril formation, we demonstrated that the diphenylalanine recognition motif of the Alzheimer’s beta-amyloid polypeptide self-assembles into ordered peptide nanotubes with a remarkable persistence length and mechanical strength. It was also demonstrated that these peptide nanotubes could serve as a mold for the fabrication of metals and building blocks of novel electrochemical platform. We also reveal that diphenylglycine, a similar analogue and the simplest aromatic peptide, forms spherical nanometric assemblies. Both the nanotubes and nanospheres assemble efficiently and have remarkable stability. The formation of either nanotubes or closed-cages by fundamentally similar peptides is consistent with a two-dimensional layer closure, as described both for carbon and inorganic nanotubes and their corresponding buckminsterfullerene and fullerene-like structures. These properties of the peptide nanostructures, taken together with their biological compatibility and remarkable thermal and chemical stability, may provide very important tools for future nanotechnology applications.

Applications, methodologies, and theories that were applied to the study of carbon and inorganic nanostructures should be of great importance for future exploration and utilization of the peptide nanostructures. We have recently demonstrated the potential use of the peptide nanotubes for biosensors applications. We also revealed the remarkable rigidity of the peptide nanotubes, which could be utilized in novel composite biomaterials. These properties of the peptide nanostructures, taken together with their biological compatibility and remarkable thermal and chemical stability, may provide very important tools for future nanotechnology applications.

The Role of Protein Folding and Stability in Type I VHL Syndrome

The recent crystal structure of pVHL-Elongin C-Elongin B complex revealed that many of the cancer-associated mutations in pVHL (most notably the mutations that lead to type I VHL syndrome) are mapped to the hydrophobic core of the protein and do not take part in the molecular interaction of pVHL with other molecules. This result clearly indicates that abnormal folding and stability play a central role in malfunction of many pVHL mutants. Nevertheless, basic information about the molecular details of the folding reaction of pVHL is still missing. There is also a lack of information on the physiological and thermodynamic stability of pVHL and the effect of cancer-related mutations on these properties. The aim of our project is to study the folding, stability, and molecular dynamics of wild-type and mutants pVHL proteins. For that purpose wild-type VHL was expressed as a GST fusion protein and was purified to >90% purity using Glutaionine Sepharose chromatography followed by Gel Filtration chromatography. As the structure of the VHL was know only at the crystal form and under cryo conditions, our first experiments were aimed toward a basic characterization of the secondary structure at physiological temperature and the thermal stability of the wild-type VHL protein using circular dichroism (CD) spectroscopy. The far UV spectrum of VHL at 37 °C is consisted with a well-folded protein with a content of both a-helices and b-sheets. The thermal melt of the VHL protein is also consistent with a stable protein have a Tm well above 37 °C. In parallel, we prepared site-directed mutants of the VHL protein at locations that are known to induce type I and type II VHL syndrome. The site-directed mutants were prepared using unique site elimination (USE) techniques. The next step of our study will include the purification of the mutant protein followed by further assessment of the folding process and the thermodynamic stability of the wild-type and mutant proteins by a variety of spectroscopic methods and by the use of calorimetry.

Molecular Characterization of a Putative Novel Toxin-Antidote System

Addiction systems are composed of pairs of toxin and antidote proteins that act in a plasmid-encoded mechanism that causes the death of their cured hosts. The mechanism of addiction is achieved by a differential stability of the toxin and antidote proteins. While the toxin proteins are stable, the antidotes are labile proteins that undergo rapid degradation. Upon plasmid curing, only the stable toxins are presence while the labile antidotes undergo degradation. This eventually leads to the death of cured cells. The differential physiological stability of the toxins and antidotes is correlated with a differential thermodynamic Stability at least in two cases: Phd and Doc, and ParE and ParD proteins. While the toxin molecules are well-folded and stable proteins, the antidote proteins are instable, partially or fully unfolded proteins. Toxin-antitoxin proteins were initially found in the context of plasmids, but genes coding addiction proteins are also present in bacterial chromosomes. It has been speculated that they may have a role in transcription-translation control or even participate in programmed cell death. Using bioinformatics tools, we have identified a novel pair of putative addiction genes in the E. coli chromosome, only one to be previously annotated, that show homology to known and predicted addiction systems. Furthermore, the pair of genes resemble classical addiction systems in its gene structure and organization. The aim of the project is to study this new operon -its function, interactions, and structure and Stability parameters. As a first step, the antidote and toxin genes were cloned together and separately under induciable T7 promoter in order to achieve high quantity levels of the proteins and assess their effect. In parallel, putative addiction genes were cloned under temperature sensitive promoter. Recently, the antidote putative protein has been partially purified using-ion exchange chromatography. The next steps of our study will include physiological characterization of putative addiction operon using the temperature sensitive clone, and biophysical characterization of the putative toxin-antitoxin proteins.

Our Recent Covers:

Books

1) Gazit, E. Plenty of Room for Biology at the Bottom: An Introduction to Bionanotechnology. Imperial College Press.

http://www.icpress.co.uk/nanosci/p465.html

[Amazon.com]

See book review in Angewandte Chemie by Bruno Samorí [review]

2) Gazit, E., and Nussinov, R. (Eds.) Nanostructure Design Protocols: Methods in Molecular Biology. Humana Press, Totowa NJ, USA. (to be published in 2008)

[Amazon.com]

Articles

1) Rapaport, D., Danin, M., Gazit, E. & Shai, Y. (1992) Membrane Interactions of the Sodium Channel S4 Fragment and Its Fluorescently-Labelled Analogues. Biochemistry 31, 8868-8875. [Full text in PDF]

2) Gazit, E. & Shai, Y. (1993) Structural and Functional Characterization of the alpha-5 Segment of Bacillus thuringiensis delta-Endotoxin. Biochemistry 32, 3429-3436. [Full text in PDF]

3) Gazit, E. & Shai, Y. (1993) Structural Characterization, Membrane Interaction, and Specific Assembly within Phospholipid Membranes of Hydrophobic Segments from Bacillus thuringiensis var. israelensis Cytolytic Toxin. Biochemistry 32, 12363-12371. [Full text in PDF]

4) Gazit, E. & Shai, Y. (1993) Membrane Interaction and Hemolytic Activity of the alpha-5 Helix of delta-endotoxin. In: Wei, Y. H., Chen, C. S., & Su, J. C. (Eds.) Recent Advances in Molecular and Biochemical Research on Proteins. (pp. 145-153) World Scientific Publishing Co. Pte. Ltd.

5) Gazit, E., Bach, D., Kerr, I. D., Sansom, M. S. P., Chejanovsky, N. & Shai, Y. (1994) The alpha-5 Segment of Bacillus thuringiensis delta -Endotoxin: In-Vitro Activity, Ion Channel Formation and Molecular Modelling. Biochem. J. 304, 895-902. [Full text in PDF]

6) Gazit, E., Lee, W.-J., Brey, P. T. & Shai, Y. (1994) Mode of Action of the Antibacterial Cecropin B2: A Spectrofluorometric Study. Biochemistry 33, 10681-10692. [Full text in PDF]

7) Gazit, E., Flajnik, M. K., Boman, H. G., Zasloff, M., Merrifield, R. B., Shal, H. G., Elsbach, P., Andreu, D., Hultmark, D. & Natori, S. (1994) On The Mechanism of Membranes Permeation by Cecropin B2 (General discussion). Ciba Found. Symp. 186, 190-196.

8) Gazit, E. & Shai, Y. (1995) The Assembly and Organization of the alpha-5 and alpha-7 Helices from the Pore-forming Domain of Bacillus thuringiensis delta-Endotoxin: Relevance to a Functional Model. J. Biol. Chem. 270, 2571-2578. [Full text in PDF]

9) Gazit, E., Boman, A., Boman, H. G. & Shai, Y. (1995) Interaction of the Mammalian Antibacterial Peptide Cecropin P1 with Phospholipid Vesicles. Biochemistry 34, 11479-11488. [Full text in PDF]

10) Gazit, E., Miller, I. R., Bigin, P., Sansom, M. S. P. & Shai, Y. (1996) Structure and Orientation of the Mammalian Antibacterial Peptide Cecropin P1 within Phospholipid Membranes. J. Mol. Biol. 258, 860-870. [Full text in PDF]

11) Gazit, E., Burshtein, N., Ellar, D. J., Saywer, T. & Shai, Y. (1997) Bacillus thuringiensis Cytolytic Toxin Associates Specifically with its Synthetic Helices A and C in the Membrane Bound State - Implications for the Assembly of Oligomeric Transmembrane Pores. Biochemistry 36, 15546-15554. [Full text in PDF]

12) Gazit, E., La Rocca, P., Sansom, M. S. P. & Shai, Y. (1998) The Structure and Organization within the Membrane of the Helices Composing the Pore-Forming Domain of Bacillus thuringiensis d-Endotoxin are Consistent with an “Umbrella-like” Structure of the Toxin Pores. Proc. Natl. Acad. Sci. USA 95, 12289-12294. [Full text in PDF]

13) Gazit, E., & Sauer, R. T. (1999) Stability and DNA Binding of the Phd Protein of Phage P1 Plasmid Addiction System. J. Biol. Chem. 274, 2652-2657. [Full text in PDF]

14) Gazit, E., & Sauer, R. T. (1999) The Doc Toxin and Phd Antidote Proteins of the Bacteriophage P1 Plasmid Addiction System Form a Heterotrimeric Complex. J. Biol. Chem. 274, 16813-16818. [Full text in PDF]

15) Azriel, R. & Gazit, E. (2001) Analysis of the Minimal Active Fragment of Islet Amyloid Polypeptide (IAPP): An Experimental Support for the Key Role for the Phenylanaline Residue in Amyloid Formation J. Biol. Chem. 276, 34156-34161. [Full text in PDF]

16) Gazit, E. (2002) The “Correctly-Folded” State of Proteins: Is it a Metastable State? Angew. Chem. Int. Ed. Engl. 41, 257-259. [Full text in PDF]

17) Gazit, E. (2002) A Possible Role for pi-stacking in the Self-Assembly of Amyloid Fibrils. FASEB J. 16, 77-83. [Full text in PDF]

18) Gazit, E. (2002) Global Analysis of Tandem Aromatic Octapeptide Repeats: The Significance of the Aromatic-Glycine Motif. Bioinformatics 18, 880-883. [Full text in PDF]

19) Reches, M., Porat, Y. & Gazit, E. (2002) Amyloid Fibrils Formation by Pentapeptide and Tetrapeptide Fragments of Human Calcitonin. J. Biol. Chem. 277, 35475-35480. [Full text in PDF]

20) Gazit, E. (2002) Mechanistic Studies of the Process of Amyloid Fibrils Formation by the use of Peptide Fragments and Analogues: Implications for the Design of Fibrillization Inhibitors. Curr. Med. Chem. 9, 1725-1735. [Full text in PDF]

21) Mazor, Y., Gilead, S., Benhar, I., & Gazit, E. (2002) Identification and Characterization of a Novel Molecular-Recognition and Self-Assembly Domain within the Islet Amyloid Polypeptide. J. Mol. Biol. 322, 1013-1024. [Full text in PDF]

22) Gur, E., Biran, D., Gazit, E., & Ron, E. Z. (2002) In vivo Aggregation of Single Enzyme Limits Growth of Escherichia Coli at Elevated Temperatures. Mol. Microbiol. 46, 1391-1397. [Full text in PDF]

23) Porat, Y., Stepensky, A., Ding, F-X, Naider, F., & Gazit, E. (2003) Completely Different Amyloidogenic Potential of Nearly Identical Peptide Fragments. Biopolymers 69, 161-164. [Full text in PDF]

24) Reches, M, & Gazit, E. (2003) Casting Metal Nanowires Within Discrete Self-Assembled Peptide Nanotubes. Science 300, 625-627. [Full text in PDF]

25) Alonso, J. C., Balsa, D., Cherny, I., Espinosa, M., Francuski, D. Gazit, E., Gerdes, K., Hitchin, E., Mart?n, M. T., Concepc?n, N. Overweg, K. Pellicer, T. Saenger, W. Welfle, H. Welfle, K., & Wells, J. (2003) Bacterial Toxin-Antitoxin Systems as Targets for the Development of Novel Antibiotics. In: Tolmasky, M, & Bonomo, R. A. (Eds.) Resistance to Antibiotics.ASM Press, Washington D.C.

26) Porat, Y., Kolusheva, S., Jelinek, R., & Gazit, E. (2003) The Human Islet Amyloid Polypeptide Forms Transient Membrane-Active Prefibrillar Assemblies. Biochemistry 42, 10971-10977. [Full text in PDF]

27) Gazit, E. (2003) Protein Folding, Unfolding, and Misfolding. In: Encyclopedia of Polymer Science and Technology. John Wiley & Sons Ltd.

28) Zanuy, D., Porat, Y., Gazit, E., & Nussinov, R. (2004) Peptide Sequence and Amyloid Formation: Molecular Simulations and Experimental Study of a Human Islet Amyloid Polypeptide Fragment and its Analogues. Structure 12, 439-55. [Full text in PDF]

29) Cherny I., & Gazit, E. (2004) The YefM Antitoxin Defines a Family of Natively Unfolded Proteins: Implications as a Novel Antibacterial Target. J. Biol. Chem. 279, 8252-8261. [Full text in PDF]

30) Reches, M., & Gazit, E. (2004) Formation of Closed-Cage Nanostructures by Self-Assembly of Aromatic Dipeptides. Nano Lett. 4, 581-585. [Full text in PDF]

31) Avisar, D., Keller, M., Gazit, E., Prudovsky, E., Sneh, B., & Zilberstein, A. (2004) The Role of Bacillus thuringiensis Cry1C and Cry1E Separate Structural Domains in the Interaction with Spodoptera littoralis Gut Epithelial Cells. J. Biol. Chem. 279, 15779 – 15786. [Full text in PDF]

32) Sutovsky, H., & Gazit, E. (2004) The Von Hippel-Lindau Tumor Suppressor Protein is Molten Globule under Native Conditions: Implications for its Physiological Activities. J. Biol. Chem. 279, 17190-17196. [Full text in PDF]

33) Gazit, E. (2004) The Role of Prefibrillar Assemblies in the Pathogenesis of Amyloid Diseases. Drugs Fut. 29, 613-619. [Full text in PDF]

34) Reches, M., & Gazit, E. (2004) Amyloidogenic Hexapeptide Fragment of Medin: Homology to Functional Islet Amyloid Polypeptide Fragments. Amyloid 11, 81-89. [Full text in PDF]

35) Gilead, S. & Gazit, E. (2004) Inhibition of Amyloid Fibril Formation by Peptide Analogues Modified with alpha-Aminoisobutyric Acid. Angew. Chem. Int. Edit. 43, 4041-4044. [Full text in PDF]

36) Porat, Y., Mazor, Y., Efrat, S. & Gazit, E. (2004) Inhibition of Islet Amyloid Polypeptide Fibril Formation: A Potential Role for Hetero-Aromatic Interactions. Biochemistry 43, 14454-14462. [Full text in PDF].

37) Gazit, E. (2005) Arrest of Amyloid Fibril Formation Associated to Type II Diabetes: Structural and Functional Links to the Mechanism of Alzheimer’s beta -Amyloid Fibrillization. Drug. Design. Rev. 2, 115-119. [Full text in PDF] 

38) Gilead, S. & Gazit, E. (2005) Self-Organization of Short Peptide Fragments: From Amyloid Fibrils to Nanoscale Supramolecular Assemblies. Supramol. Chem. 17 , 87-92. [Full text in PDF].

39) Gazit, E. Self-Assembly of Short Peptides for Nanotechnological Applications. In: Shoseyov, O., and Levy, I. (eds.) NanoBioTechnology: BioInspired Device and Materials of the Future. Humana Press, Totowa NJ, USA. (pp. 385-395). ISBN 1-58829-894-9. [Amazon.com]

40) Yemini, M., Reches, M., Rishpon, J., & Gazit, E. (2005) Novel Electrochemical Biosensing Platform Using Self-Assembled Peptide Nanotubes. Nano Lett. 5, 183-186. [Full text in PDF].

41) Carny, O., & Gazit, E. (2005) A Model for the Role of Short Self-Assembled Peptides in the very Early Stages of the Origin of Life. FASEB J. 19, 1051-1055. [Full text in PDF].

42) Gazit. E. (2005) Novel Antibacterial Drug Candidates based on Toxin-Antitoxin Modules. In: Ingemansson, K. T. and Knezevic, M. (eds.). EUR 20602 – 100 Technology Offers Stemming from EU Biotechnology RTD Results. Office of the European Commission. ISBN 92-894-4812-1 (pp. 246-248).

43) Gazit, E. (2005) Dalle Sofferenze del Morbo di Alzheimer alle Meraviglie delle Nanotecnologie (From the Misery of Alzheimer's Disease to the Wonders of Nanotechnology), KOS, Milan, Italy. 225, 62-64 (in Italian).

44) Gilead, S., and Gazit, E. The Role of Aromatic Interactions in Folding, Stability, and Molecular Recognition of Proteins and Polypeptides. In: Uversky, V. N. and Permyakov, E.A. (eds.). Protein Structures: Methods in Protein Structure and Stability Analysis. Nova Science Publishers, Hauppauge NY, USA. ISBN: 1-60021-705-2.

45) Reches, M., & Gazit, E. (2005) Self-assembly of Peptide Nanotubes and Amyloid-Like Structures by Charged-Termini Capped Diphenylalanine Peptide Analogues. Israel J. Chem. 45, 363-371. [Full text in PDF]

46) Colombo, G., Daidone, I., Gazit, E. , Amadei, A., & Di Nola, A. (2005) Molecular Dynamics Simulation of the Aggregation of the Core Recognition Motif of the Islet Amyloid Polypeptide in Explicit Water. Proteins 59, 519-527. [Full text in PDF]

47) Yemini, M., Reches, M., Gazit, E., & Rishpon, J. (2005) Peptide Nanotubes Modified Electrodes for Enzyme-Biosensors Applications. Anal. Chem. 77, 5155-5159. [Full text in PDF]

48)  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. [Full text in PDF]

49)  Tsai, H-H., Reches, M., Tsai, C-J., Gunasekaran, K., Gazit, E. & Nussinov, R. (2005) Energy Landscape of Amyloidogenic Peptide Oligomerization by Parallel-tempering Molecular Dynamics Simulation: Significant Role of Asn Ladder. Proc. Natl. Acad. Sci. USA 102 , 8174-8179. [Full text in PDF]

50) Cherny , I., Rockah, L. & Gazit, E. (2005) The YoeB Toxin is a Folded Protein that Forms a Physical Complex with the Unfolded YefM Antitoxin: Implications for a Structural-based Differential Stability of Toxin-antitoxin Systems. J. Biol. Chem. 280, 30063-30072. [Full text in PDF]

51) Cherny, I., Rockah, L., Levy-Nissenbaum, O., Gophna, U., Ron, E. Z., & Gazit, E. (2005) The Formation of Curli Amyloid Fibrils is Mediated by Prion-like Peptide Repeats. J. Mol. Biol. 352, 245-252. [Full text in PDF]

52) Motta, A., Reches, M., Pappalardo, L., Andreotti, G., & Gazit, E. (2005) The Preferred Conformation of the Tripeptide Ala-Phe-Ala in Water is an Inverse Gamma-turn: Implications for Protein Folding and Drug Design. Biochemistry 44, 14170-14178. [Full text in PDF]

53) Gazit, E. (2005) Mechanisms of Amyloid Fibril Self-Assembly and Inhibition: Model Short Peptides as a Key Research Tool. FEBS J. 272, 5971-5978. [Full text in PDF]

54) Porat, Y., Abramowitz, A., & Gazit, E. (2006) Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism. Chem. Biol. Drug Des. 67, 27-37. [Full text in PDF]

55) Reches, M., & Gazit, E. (2006) Molecular Self-Assembly of Peptide Nanostructures: Mechanism of Association and Potential Uses. Curr. Nanoscience 2, 105-111. [Full text in PDF]

56) Adler-Abramovich, L., Reches, M., Sedman, V. L., Allen, S., Tendler, S. J. B., & Gazit, E. (2006) Thermal and Chemical Stability of Diphenylalanine Peptide Nanotubes: Implications for Nanotechnological Applications. Langmuir 22,1313-1320. [Full text in PDF]

57) Reches, M., & Gazit, E. (2006) Designed Aromatic Homo-Dipeptides: Formation of Ordered Nanostructures and Potential Nanotechnological Applications. Phys. Biol. 3, S10-S19. [Full text in PDF]

58) Mahler, A., Reches, M., Rechter, M., Cohen, S. & Gazit, E. (2006). Rigid, Self-Assembled Hydrogel Composed of a Modified Aromatic Dipeptide. Adv. Mater. 18, 1365 - 1370.  [Full text in PDF]

59) Cohen, T., Frydman-Marom, A., Rechter, M., & Gazit, E. (2006) Inhibition of Amyloid Fibril Formation and Cytotoxicity by Hydroxy-Indole Derivatives. Biochemistry 45, 4727 - 4735. [Full text in PDF]

60) Gazit, E. (2006) Nanoscience and Nanotechnology as Research and Development Tools for Biology and Medicine . Nanomedicine 1, 135-137 [Full text in PDF]

61) Sedman, V.L., Adler-Abramovich, L., Allen, S., Gazit, E., & Tendler, S. J. B. (2006) Direct Observation of the Release of Phenylalanine from Diphenylalanine Nanotubes. J. Am. Chem. Soc. 128, 6903-6908. [Full text in PDF]

62) Avidan-Shpalter, C., & Gazit, E. (2006) The Early Stages of Amyloid Formation: Biophysical and Structural Characterization of Calcitonin Pre-fibrillar Assemblies. Amyloid 13, 216-225. [Full text in PDF]

63) Gilead, S., Wolfenson, H., & Gazit, E. (2006) Physiological Mechanism for Preventing Amyloid Formation: The Molecular Recognition between Islet Amyloid Polypeptide and Insulin. Angew. Chem. Int. Ed. Engl. 45, 6476-6480. [Full text in PDF]

64) Carny, O., Shalev, D., & Gazit, E. (2006) Fabrication of Coaxial Metal Nanowires Using Self-Assembled Peptide Nanotube Scaffold. Nano Lett. 6, 1594-1597. [Full text in PDF]

65) Gazit, E. (2006) From Green Bacteria to Human Dementia: Novel Models for the Discovery of Amyloid Assembly Inhibitors. ACS Chem. Biol. 1, 417-419. [Full text in PDF]

66) Levy, M. Garmy, N. Gazit, E., & Fantini, J. (2006) The Minimal Amyloid-Forming Fragment of the Islet Amyloid Polypeptide is a Glycolipid-Binding Domain. FEBS J. 273, 5724-5735. [Full text in PDF]

67) Gazit, E. & Tendler, S. J. B. (2006) Analytical Techniques - Piecing together Biornolecular Self-Assembly. Curr. Opin. Chem. Biol. 10, 385-386 [Full text in PDF]

68) Gazit, E. (2006) Special issue on supramolecular biochemical assemblies - Preface. Supramol. Chem.18, 387-388 [Full text in PDF]

69) Reches, M., & Gazit, E. (2006) Controlled Patterning of Aligned Self-Assembled Peptide Nanotubes. Nature Nanotech. 1, 195-200. [Full text in PDF]

70) Nieto, C., Cherny, I., Khoo, S. K., de Lacoba, M. G., Chan, W. T., Yeo, C. C., Gazit, E., & Espinosa, M. (2007) The YefM-YoeB Toxin-Antitoxin Systems of Escherichia coli and Streptococcus pneumoniae: Functional and Structural Correlation. J. Bact. 189, 1266-1278. [Full text in PDF]

71) Reches, M. and Gazit, E. Peptide Nanomaterials: Self-Assembling Peptides as Building Blocks for Novel Materials. In: Nanomaterials Chemistry: Novel aspects and New Directions edited by Rao, C.N.R., Mueller, A., and Cheetham, A.K. Wiley-VCH, Weinheim Germany (pp 171-183). ISBN 3-5273-1664-7. [Amazon.com]

72) Gazit E. (2007) Application of Biomolecules for the Synthesis of Inorganic Nanowires. FEBS J.  274, 317-322. [Full text in PDF]

73) Ghosh, S., Reches, M., Gazit, E., Verma, S. (2007) Bio-Inspired Design of Nano-Cages by Triskelion Self-Assembling Peptide Elements. Angew. Chem. Int. Ed. Engl. 46, 2002-2004 . [Full text in PDF]

74) Reches, M., and Gazit, E. (2007) Biological and Chemical Decoration of Peptide Nanostructures via Biotin-Avidin Interaction. J. Nanosci. Nanotechnol. 7, 2239–2245. [Full text in PDF]

75) Gazit, E., della Bruna, P., Pieraccini S, & Colombo, G. (2007) The Molecular Dynamics of Assembly of the Ubiquitous Aortic Medial Amyloidal Medin Fragment. J. Mol. Graph. Model. 25, 903-911. [Full text in PDF]

76) Shoval, H., Lichtenberg, D., & Gazit, E. (2007) The Molecular Mechanisms of the Anti-Amyloidogenic and Fibril-Destabilizing Effects of Phenols and Polyphenols. Amyloid 14, 73-87. [Full text in PDF]

77) Colmbo, G., Soto, P. and Gazit, E. (2007) Self Aggregating Systems and Peptides and their Possible Use. Trends Biotechnol. 25, 211-218 . [Full text in PDF]

78) Gazit, E. (2007) Self Assembly of Short Aromatic Peptides into Amyloid Fibrils and Related Nanostructures. Prion 1, 32-35. [Full text in PDF]

79) Gazit E. (2007) Self-Assembled Peptide Nanostructures: The Design of Molecular Building Blocks and their Technological Utilization. Chem. Soc. Rev. 36, 1263–1269. [Full text in PDF]

80) Adler-Abramovich, L., Perry, R. Sagi, A., Gazit, E., and Shabat, D. (2007) Controlled Assembly of Peptide Nanotubes Triggered by Enzymatic Activation of Self-Immolative Dendrimers. ChemBioChem  8, 859-862. [Full text in PDF]

81) Hendler, N., Sidelman, N., Reches, M., Gazit, E., Rosenberg, Y., and Richter, S. (2007) Formation of Well-Organized Self-Assembled Films From Peptide Nanotubes. Adv. Mater. 11, 1485-1488 [Full text in PDF]

82) Hill, R. J. A., Sedman, V. L., Allen, S., Williams, P., Paoli, M., Adler-Abramovich, L., Gazit, E., Eaves, L., and Tendler, S. J. B. (2007) Investigating and Understanding the Direct Alignment of Aromatic Peptide Nanotubes by Magnetic Fields. Adv. Mater. 19, 4474 - 4479. [Full text in PDF]

83) Cherny, I., Overgaard, M., Borch, J., Bram, Y., Gerdes, K. and Gazit, E. (2007) Structural and Thermodynamic Characterization of the Escherichia Coli RelBE Toxin-Antitoxin System: Indication for Functional Role of Differential Stability. Biochemistry 43, 12152-12163 .

84) Sopher, N. B., Abrams Z. R., Reches, M., Gazit, E. and Hanein, Y. (2007) Integrating Peptide Nanotubes in Micro-Fabrication Processes. J. Micromech. Microeng. 11, 2360-2365.

85) Cherny I., and Gazit, E. (2008) The Bright Side of Amyloids: Not Only Pathological Agents but also Ordered Nano-Scale Materials. Angew. Chem. Int. Ed. Engl. 47, 4062-4069.

86) Adler-Abramovich, L., and Gazit, E. (2008) Controlled pattering of peptide nanotubes and nanospheres using inkjet printing technology. J. Pep. Sci. 14, 217-223.

87) Soreq H. and Gazit, E. (2008) The structural basis of amyloid formation. Curr. Alzheimer Res. 5, 232.

88) Gazit, E. (2008) Bioactive nanostructures branch out. Nature Nanotech. 1, 8-9.

89) Adler-Abramovich, L., Aronov, D., Gazit, E., and Rosenman, G. (2008) Patterned Arrays of Ordered Peptide
Nanostructures. J. Nanosci. Nanotech. (in press).

90) Gilead, S. and Gazit, E. (2008) The role of the 14-20 domain of the islet amyloid polypeptide in amyloid formation. Exp. Diabet. Res. 2008: 256954.

91) Shoval, H., Weiner, L., Gazit, E., Levy, M., Pinchuk, I. and Lichtenberg, D. (2008) Polyphenol-induced dissociation of various amyloid fibrils results in a methionine-independent formation of ROS. Biochim. Biophys. Acta (in press).

92) Rambold, A. S., Miesbauer, M., Olschewski, D., Seidel, R., Riemer, C., Smale, L., Brumm, L., Levy, M., Gazit, E. Oesterhelt, D., Baier, M., Becker, C. F. W., Engelhard, M., Winklhofer, K. F., and Tatzelt, J. (2008) Green tea extracts interfere with the stress-protective activity of PrPC and the formation of PrPSc. J. Neurochem. 107, 218-229.

93) Garcia-Pino, A., Dao-Thi, M. H., Gazit, E., Magnuson, R. D., Wyns, L., Loris, R. (2008) Crystallization of Doc and the Doc:Phd toxin-antitoxin complex (in press).

94) Frydman-Marom, A. Rechter, M. Shefler, I., Bram, Y., Shalev, D. E., and Gazit, E. (2008) Cognitive Performance Recovery of Alzheimer's Disease Model Mice by Modulating Early Soluble Amyloidal Assemblies. Angew. Chem. Int. Ed. Engl. (accepted).

Gazit Group

May 2007