Claudio Soto University of Texas Medical School at Houston
Posted:
This is an interesting article on the production of nanotubes by polymerization of a dipeptide inspired by the central hydrophobic region of the amyloid-β (Aβ) protein. The authors provide a detailed description of why they focused on Phe-Phe as the building block for the nanotubes. They quote previous work showing that the fragment LVFFA seems essential for Aβ fibril formation and has been used by several groups to produce peptide inhibitors of fibrillogenesis.
This article is a nice continuation of several previous studies by this group showing that aromatic residues (in particular, phenylalanine) are present and play a key role in fibrillogenesis of many amyloid-forming peptides, including Aβ, amylin, serum amyloid-A, gelsolin, calcitonin, etc. This idea is consistent with our recent data published this month (Adessi et al., 2003) indicating that the two phenylalanines are critical for binding and activity of Aβ aggregation inhibitors.
The work of Gazit's group is very important to understanding the mechanism of amyloid formation and to design aggregation inhibitors. In a previous article, they proposed an intriguing new model for amyloid formation driven by p-stacking interactions between aromatic residues (Gazit, 2002).
In addition, the present article is interesting because it expands our knowledge of peptide aggregation for building biomaterials, which allows us to see protein aggregation not only as a stubborn problem in biotechnological protein production and as the potential cause of pathology in protein misfolding disorders, but also as a promising application in nanotechnology. Another article published this month by Susan Lindquist's group points in the same direction by showing that polymerization of fragments of the yeast prion Sup35 can make good nanowires (Scheibel et al., 2003). It looks like the research in Alzheimer's amyloidosis will have an impact not only on closely related subjects (such as pathology of other protein misfolding disorders), but also in the quite distant field of nanotechnology!
References:
Adessi C, Frossard MJ, Boissard C, Fraga S, Bieler S, Ruckle T, Vilbois F, Robinson SM, Mutter M, Banks WA, Soto C.
Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer's disease.
J Biol Chem. 2003 Apr 18;278(16):13905-11.
PubMed.
Gazit E.
A possible role for pi-stacking in the self-assembly of amyloid fibrils.
FASEB J. 2002 Jan;16(1):77-83.
PubMed.
Scheibel T, Parthasarathy R, Sawicki G, Lin XM, Jaeger H, Lindquist SL.
Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition.
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4527-32.
PubMed.
This study of the remarkable properties of peptides, initially investigated because they might yield insights into Alzheimer's disease, provides a vivid example of how biological research can take the most unexpected turns, with potential benefits never dreamed of at the start.
Gazit and his student, Meital Reches, have achieved something others have tried for many years, from a complete different route. This again demonstrates the crucial aspect of the curiosity-driven research that can eventually alter a concept or start up new industry. Funding for basic science has been eroded due to short-sightedness of many governmental funding agencies and econminc down turn. This discovery should remind all of us the power of basic and curiosity driven research, the well springs of breakthrough advances in both science and technology. Sir John Maddox, the former Editor of Nature, wrote at the end of last century, December 1999 in Scientific American "The unexpected to come:The most important discoveries of the next 50 years are likely to be ones of which we cannot now even conceive". How correct he was. Our research have also taken the same route several years ago.
References:
Zhang S, Holmes T, Lockshin C, Rich A.
Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane.
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3334-8.
PubMed.
Vauthey S, Santoso S, Gong H, Watson N, Zhang S.
Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles.
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5355-60. Epub 2002 Apr 2
PubMed.
Comments
University of Texas Medical School at Houston
This is an interesting article on the production of nanotubes by polymerization of a dipeptide inspired by the central hydrophobic region of the amyloid-β (Aβ) protein. The authors provide a detailed description of why they focused on Phe-Phe as the building block for the nanotubes. They quote previous work showing that the fragment LVFFA seems essential for Aβ fibril formation and has been used by several groups to produce peptide inhibitors of fibrillogenesis.
This article is a nice continuation of several previous studies by this group showing that aromatic residues (in particular, phenylalanine) are present and play a key role in fibrillogenesis of many amyloid-forming peptides, including Aβ, amylin, serum amyloid-A, gelsolin, calcitonin, etc. This idea is consistent with our recent data published this month (Adessi et al., 2003) indicating that the two phenylalanines are critical for binding and activity of Aβ aggregation inhibitors.
The work of Gazit's group is very important to understanding the mechanism of amyloid formation and to design aggregation inhibitors. In a previous article, they proposed an intriguing new model for amyloid formation driven by p-stacking interactions between aromatic residues (Gazit, 2002).
In addition, the present article is interesting because it expands our knowledge of peptide aggregation for building biomaterials, which allows us to see protein aggregation not only as a stubborn problem in biotechnological protein production and as the potential cause of pathology in protein misfolding disorders, but also as a promising application in nanotechnology. Another article published this month by Susan Lindquist's group points in the same direction by showing that polymerization of fragments of the yeast prion Sup35 can make good nanowires (Scheibel et al., 2003). It looks like the research in Alzheimer's amyloidosis will have an impact not only on closely related subjects (such as pathology of other protein misfolding disorders), but also in the quite distant field of nanotechnology!
References:
Adessi C, Frossard MJ, Boissard C, Fraga S, Bieler S, Ruckle T, Vilbois F, Robinson SM, Mutter M, Banks WA, Soto C. Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer's disease. J Biol Chem. 2003 Apr 18;278(16):13905-11. PubMed.
Gazit E. A possible role for pi-stacking in the self-assembly of amyloid fibrils. FASEB J. 2002 Jan;16(1):77-83. PubMed.
Scheibel T, Parthasarathy R, Sawicki G, Lin XM, Jaeger H, Lindquist SL. Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4527-32. PubMed.
Whitehead Institute for Biomedical Research
This study of the remarkable properties of peptides, initially investigated because they might yield insights into Alzheimer's disease, provides a vivid example of how biological research can take the most unexpected turns, with potential benefits never dreamed of at the start.
Gazit and his student, Meital Reches, have achieved something others have tried for many years, from a complete different route. This again demonstrates the crucial aspect of the curiosity-driven research that can eventually alter a concept or start up new industry. Funding for basic science has been eroded due to short-sightedness of many governmental funding agencies and econminc down turn. This discovery should remind all of us the power of basic and curiosity driven research, the well springs of breakthrough advances in both science and technology. Sir John Maddox, the former Editor of Nature, wrote at the end of last century, December 1999 in Scientific American "The unexpected to come:The most important discoveries of the next 50 years are likely to be ones of which we cannot now even conceive". How correct he was. Our research have also taken the same route several years ago.
References:
Zhang S, Holmes T, Lockshin C, Rich A. Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3334-8. PubMed.
Vauthey S, Santoso S, Gong H, Watson N, Zhang S. Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5355-60. Epub 2002 Apr 2 PubMed.
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