Substoichiometric inhibition of Aβ1-40 aggregation by a tandem Aβ40-1-Gly8-1-40 peptide

Sourajit M. Mustafi; Kanchan Garai; Scott L. Crick; Berevan Baban; Carl Frieden

doi:10.1016/j.bbrc.2010.05.144

Substoichiometric inhibition of Aβ_1-40 aggregation by a tandem Aβ_{40-1-Gly8-1-40} peptide

Sourajit M. Mustafi
, Kanchan Garai
, Scott L. Crick
, Berevan Baban
, Carl Frieden

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Aβ peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Aβ_1-40 fibrillization as a tandem dimeric construct consisting of Aβ_40-1 (reverse sequence) linked to Aβ_1-40 via an eight residue glycine linker. At molar ratios of the tandem peptide to Aβ_1-40 of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.

Original language	English
Pages (from-to)	509-512
Number of pages	4
Journal	Biochemical and Biophysical Research Communications
Volume	397
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2010.05.144
State	Published - Jul 2010

Keywords

Atomic force microscopy
Fibrillization
Reverse sequence
ThioflavinT

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10.1016/j.bbrc.2010.05.144

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title = "Substoichiometric inhibition of Aβ1-40 aggregation by a tandem Aβ40-1-Gly8-1-40 peptide",

abstract = "Aβ peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Aβ1-40 fibrillization as a tandem dimeric construct consisting of Aβ40-1 (reverse sequence) linked to Aβ1-40 via an eight residue glycine linker. At molar ratios of the tandem peptide to Aβ1-40 of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.",

keywords = "Atomic force microscopy, Fibrillization, Reverse sequence, ThioflavinT",

author = "Mustafi, \{Sourajit M.\} and Kanchan Garai and Crick, \{Scott L.\} and Berevan Baban and Carl Frieden",

note = "Funding Information: This work was supported in part by National Institute of Health Grant DK13332 and a Washington University Hope Center Grant. Mass spectrometry provided by the Washington University Mass Spectrometry Resource, a NIH Research Source (Grant No. P41RR0954). The authors also thank Mr. Brain Gau, of Mass Spectrometry facility, Department of Chemistry, Washington University, for his help in recording the Mass Spectra of the Tandem Peptide. ",

year = "2010",

month = jul,

doi = "10.1016/j.bbrc.2010.05.144",

language = "English",

volume = "397",

pages = "509--512",

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T1 - Substoichiometric inhibition of Aβ1-40 aggregation by a tandem Aβ40-1-Gly8-1-40 peptide

AU - Mustafi, Sourajit M.

AU - Garai, Kanchan

AU - Crick, Scott L.

AU - Baban, Berevan

AU - Frieden, Carl

N1 - Funding Information: This work was supported in part by National Institute of Health Grant DK13332 and a Washington University Hope Center Grant. Mass spectrometry provided by the Washington University Mass Spectrometry Resource, a NIH Research Source (Grant No. P41RR0954). The authors also thank Mr. Brain Gau, of Mass Spectrometry facility, Department of Chemistry, Washington University, for his help in recording the Mass Spectra of the Tandem Peptide.

PY - 2010/7

Y1 - 2010/7

N2 - Aβ peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Aβ1-40 fibrillization as a tandem dimeric construct consisting of Aβ40-1 (reverse sequence) linked to Aβ1-40 via an eight residue glycine linker. At molar ratios of the tandem peptide to Aβ1-40 of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.

AB - Aβ peptides aggregate to form insoluble and neurotoxic fibrils associated with Alzheimer's disease. Inhibition of the aggregation has been the subject of numerous studies. Here we describe a novel, substoichiometric inhibitor of Aβ1-40 fibrillization as a tandem dimeric construct consisting of Aβ40-1 (reverse sequence) linked to Aβ1-40 via an eight residue glycine linker. At molar ratios of the tandem peptide to Aβ1-40 of 1:10 to 1:25 inhibition of fibrillization, as measured by ThioflavinT, was observed. We postulate that the tandem construct binds to a fibrillar intermediate but the reverse sequence delays or prevents further monomer association.

KW - Atomic force microscopy

KW - Fibrillization

KW - Reverse sequence

KW - ThioflavinT

UR - https://www.scopus.com/pages/publications/77954218832

U2 - 10.1016/j.bbrc.2010.05.144

DO - 10.1016/j.bbrc.2010.05.144

M3 - Article

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AN - SCOPUS:77954218832

SN - 0006-291X

VL - 397

SP - 509

EP - 512

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

ER -

Substoichiometric inhibition of Aβ_1-40 aggregation by a tandem Aβ_{40-1-Gly8-1-40} peptide

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Keywords

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