Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity

Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity

The amyloid protein aggregation associated with diseases such as Alzheimer’s, Parkinson’s, and type II diabetes (among many others), features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibers. The variation in the amino acid sequences...

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Main Authors: Cheng, Pin-Nan, Liu, Cong, Zhao, Minglei, Eisenberg, David, Nowick, James S.
Format: Online
Language:English
Published: 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481199/
id pubmed-3481199
recordtype oai_dc
spelling pubmed-34811992013-05-01 Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity Cheng, Pin-Nan Liu, Cong Zhao, Minglei Eisenberg, David Nowick, James S. Article The amyloid protein aggregation associated with diseases such as Alzheimer’s, Parkinson’s, and type II diabetes (among many others), features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibers. The variation in the amino acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from Aβ associated with Alzheimer’s disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson’s disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles. 2012-09-09 2012-11 /pmc/articles/PMC3481199/ /pubmed/23089868 http://dx.doi.org/10.1038/nchem.1433 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Cheng, Pin-Nan
Liu, Cong
Zhao, Minglei
Eisenberg, David
Nowick, James S.
spellingShingle Cheng, Pin-Nan
Liu, Cong
Zhao, Minglei
Eisenberg, David
Nowick, James S.
Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
author_facet Cheng, Pin-Nan
Liu, Cong
Zhao, Minglei
Eisenberg, David
Nowick, James S.
author_sort Cheng, Pin-Nan
title Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
title_short Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
title_full Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
title_fullStr Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
title_full_unstemmed Amyloid β-Sheet Mimics that Antagonize Amyloid Aggregation and Reduce Amyloid Toxicity
title_sort amyloid β-sheet mimics that antagonize amyloid aggregation and reduce amyloid toxicity
description The amyloid protein aggregation associated with diseases such as Alzheimer’s, Parkinson’s, and type II diabetes (among many others), features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibers. The variation in the amino acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from Aβ associated with Alzheimer’s disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson’s disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481199/
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