Abstract
We describe the directed evolution of a miniature β-sheet protein for targeting β-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our β-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable β-sheet. TJ10 was found to prevent β-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent β-sheet chemical template for effectively targeting β-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 14456-14457 |
| Number of pages | 2 |
| Journal | Journal of the American Chemical Society |
| Volume | 128 |
| Issue number | 45 |
| DOIs | |
| State | Published - Nov 15 2006 |
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ASJC Scopus subject areas
- Chemistry(all)
Cite this
Inhibition of β-amyloid fibrillization by directed evolution of a β-sheet presenting miniature protein. / Smith, Thaddeus J.; Stains, Cliff I.; Meyer, Scott C.; Ghosh, Indraneel.
In: Journal of the American Chemical Society, Vol. 128, No. 45, 15.11.2006, p. 14456-14457.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of β-amyloid fibrillization by directed evolution of a β-sheet presenting miniature protein
AU - Smith, Thaddeus J.
AU - Stains, Cliff I.
AU - Meyer, Scott C.
AU - Ghosh, Indraneel
PY - 2006/11/15
Y1 - 2006/11/15
N2 - We describe the directed evolution of a miniature β-sheet protein for targeting β-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our β-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable β-sheet. TJ10 was found to prevent β-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent β-sheet chemical template for effectively targeting β-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.
AB - We describe the directed evolution of a miniature β-sheet protein for targeting β-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our β-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable β-sheet. TJ10 was found to prevent β-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent β-sheet chemical template for effectively targeting β-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.
UR - http://www.scopus.com/inward/record.url?scp=33750968798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750968798&partnerID=8YFLogxK
U2 - 10.1021/ja065557e
DO - 10.1021/ja065557e
M3 - Article
C2 - 17090018
AN - SCOPUS:33750968798
VL - 128
SP - 14456
EP - 14457
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 45
ER -