Inhibition of β-amyloid fibrillization by directed evolution of a β-sheet presenting miniature protein

Thaddeus J. Smith, Cliff I. Stains, Scott C. Meyer, Indraneel Ghosh

Research output: Contribution to journalArticle

36 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)14456-14457
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number45
DOIs
StatePublished - Nov 15 2006

Fingerprint

Amyloid
Proteins
Protein Transport
Circular dichroism spectroscopy
Denaturation
Circular Dichroism
Oligomers
Immunoglobulins
Assays
Spectrum Analysis
Alzheimer Disease
Hot Temperature
Inhibition (Psychology)
Experiments
saiko-keishi-to

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 journalArticle

@article{725449f97e7a4270b9e350f219912f48,
title = "Inhibition of β-amyloid fibrillization by directed evolution of a β-sheet presenting miniature protein",
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.",
author = "Smith, {Thaddeus J.} and Stains, {Cliff I.} and Meyer, {Scott C.} and Indraneel Ghosh",
year = "2006",
month = "11",
day = "15",
doi = "10.1021/ja065557e",
language = "English (US)",
volume = "128",
pages = "14456--14457",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "45",

}

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

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 -