Evidence map›Paper›PMID 25751170›Full record

ArticleThe journal of physical chemistry. B2015

Amyloid β-protein assembly: The effect of molecular tweezers CLR01 and CLR03.

Xueyun Zheng, Deyu Liu, Frank-Gerrit Klärner, Thomas Schrader, Gal Bitan, Michael T Bowers

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of physical chemistry. B, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 77 citations in OpenAlex.

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  15. Acetylation of AβACS chemical neuroscience · 2020
    Article
  16. NMR Spectroscopy of supramolecular chemistry on protein surfaces.Beilstein journal of organic chemistry · 2020
    Review
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Xueyun Zheng†Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
Deyu Liu†Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
Frank-Gerrit Klärner‡Institute of Organic Chemistry, University of Duisburg-Essen, Essen 45117, Germany.
Thomas Schrader‡Institute of Organic Chemistry, University of Duisburg-Essen, Essen 45117, Germany.
Gal Bitan§Department of Neurology, David Geffen School of Medicine, Brain Research Institute, and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90095, United States.
Michael T Bowers†Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, United States.
University of California, Santa Barbara · USUniversity of Duisburg-Essen · DEUniversity of California, Los Angeles · US

Funding

Amyloid Beta-Protein: Wild Type and Familial Mutant Assembly and InhibitionR01AG047116 · NIA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI BOWERS, MICHAEL THOMAS · 2013 to 2016
$1.8M
NIA NIH HHS R01 AG047116NIA NIH HHS R01AG047116
6 · The paper itself

Abstract

The early oligomerization of amyloid β-protein (Aβ) has been shown to be an important event in the pathology of Alzheimer's disease (AD). Designing small molecule inhibitors targeting Aβ oligomerization is one attractive and promising strategy for AD treatment. Here we used ion mobility spectrometry coupled to mass spectrometry (IMS-MS) to study the different effects of the molecular tweezers CLR01 and CLR03 on Aβ self-assembly. CLR01 was found to bind to Aβ directly and disrupt its early oligomerization. Moreover, CLR01 remodeled the early oligomerization of Aβ42 by compacting the structures of dimers and tetramers and as a consequence eliminated higher-order oligomers. Unexpectedly, the negative-control derivative, CLR03, which lacks the hydrophobic arms of the tweezer structure, was found to facilitate early Aβ oligomerization. Our study provides an example of IMS as a powerful tool to study and better understand the interaction between small molecule modulators and Aβ oligomerization, which is not attainable by other methods, and provides important insights into therapeutic development of molecular tweezers for AD treatment.

Indexed as

Amyloid beta-PeptidesBridged-Ring CompoundsModels, MolecularOrganophosphatesOrganophosphorus CompoundsPeptide FragmentsProtein MultimerizationProtein Structure, SecondaryAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Bridged-Ring CompoundsCLR01 compoundCLR03 compoundOrganophosphatesOrganophosphorus CompoundsPeptide Fragments

Identifiers

PMID25751170
PMCPMC4415044
OpenAlexW1981310330

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.