Highly sensitive amyloid detection enabled by thioflavin T dimers

被引：42

作者：

Qin, Luoheng ^{[1
]}

Vastl, Julian ^{[1
]}

Gao, Jianmin ^{[1
]}

机构：

[1] Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA

来源：

MOLECULAR BIOSYSTEMS | 2010年 / 6卷 / 10期

关键词：

ALZHEIMERS-DISEASE; HIGH-AFFINITY; FIBRILS; BINDING; PROTEIN; BRAIN; DERIVATIVES; MECHANISM; MARKERS; SURFACE;

D O I：

10.1039/c005255h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fluorescent molecules that specifically target amyloid structures are highly desirable for amyloid research. Herein, we show a dimeric design of thioflavin T improves its binding affinity to Ab amyloid by up to 70 fold, while not sacrificing the specificity and the "light-up" feature upon amyloid binding.

引用

页码：1791 / 1795

页数：5

共 21 条

[1] Direct observation of amyloid growth monitored by total internal reflection fluorescence microscopy [J].

Ban, Tadato ;

Goto, Yuji .

AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT C, 2006, 413 :91-102

[2] Molecular Mechanism of Thioflavin-T Binding to the Surface of β-Rich Peptide Self-Assemblies [J].

Biancalana, Matthew ;

Makabe, Koki ;

Koide, Akiko ;

Koide, Shohei .

JOURNAL OF MOLECULAR BIOLOGY, 2009, 385 (04) :1052-1063

[3] Oxidative metabolites accelerate Alzheimer's amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation [J].

Bieschke, J ;

Zhang, QH ;

Powers, ET ;

Lerner, RA ;

Kelly, JW .

BIOCHEMISTRY, 2005, 44 (13) :4977-4983

[4] Protofibrils, pores, fibrils, and neurodegeneration: Separating the responsible protein aggregates from the innocent bystanders [J].

Caughey, B ;

Lansbury, PT .

ANNUAL REVIEW OF NEUROSCIENCE, 2003, 26 :267-298

[5] Inhibiting protein-amyloid interactions with small molecules: A surface chemistry approach [J].

Inbar, P ;

Yang, J .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (04) :1076-1079

[6] Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B [J].

Klunk, WE ;

Engler, H ;

Nordberg, A ;

Wang, YM ;

Blomqvist, G ;

Holt, DP ;

Bergström, M ;

Savitcheva, I ;

Huang, GF ;

Estrada, S ;

Ausén, B ;

Debnath, ML ;

Barletta, J ;

Price, JC ;

Sandell, J ;

Lopresti, BJ ;

Wall, A ;

Koivisto, P ;

Antoni, G ;

Mathis, CA ;

Långström, B .

ANNALS OF NEUROLOGY, 2004, 55 (03) :306-319

[7] Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain [J].

Klunk, WE ;

Wang, YM ;

Huang, GF ;

Debnath, ML ;

Holt, DP ;

Mathis, CA .

LIFE SCIENCES, 2001, 69 (13) :1471-1484

[8]

Klunk WE, 1999, METHOD ENZYMOL, V309, P285

[9] The binding of thioflavin-T to amyloid fibrils: localisation and implications [J].

Krebs, MRH ;

Bromley, EHC ;

Donald, AM .

JOURNAL OF STRUCTURAL BIOLOGY, 2005, 149 (01) :30-37

[10] Diffusible, nonfibrillar ligands derived from Aβ1-42 are potent central nervous system neurotoxins [J].

Lambert, MP ;

Barlow, AK ;

Chromy, BA ;

Edwards, C ;

Freed, R ;

Liosatos, M ;

Morgan, TE ;

Rozovsky, I ;

Trommer, B ;

Viola, KL ;

Wals, P ;

Zhang, C ;

Finch, CE ;

Krafft, GA ;

Klein, WL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6448-6453

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