Evidence map›Paper›PMID 27029347›Full record

ArticleThe Biochemical journal2016

High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer β-amyloid peptide.

Sabine Rauth, Dominik Hinz, Michael Börger, Markus Uhrig, Manuel Mayhaus, Matthias Riemenschneider, Arne Skerra

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

13 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. AnticalinBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018
    Review
  11. Article
  12. Article
  13. Nanobodies: Chemical Functionalization Strategies and Intracellular Applications.Angewandte Chemie (International ed. in English) · 2018
    Review
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

7 authors at 3 institutions in 1 country.

Sabine RauthMunich Center for Integrated Protein Science (CIPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, 85354 Freising (Weihenstephan), Germany.
Dominik HinzMunich Center for Integrated Protein Science (CIPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, 85354 Freising (Weihenstephan), Germany.
Michael BörgerMunich Center for Integrated Protein Science (CIPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, 85354 Freising (Weihenstephan), Germany.
Markus UhrigDepartment of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Manuel MayhausDepartment of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Matthias RiemenschneiderDepartment of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany.
Arne SkerraMunich Center for Integrated Protein Science (CIPS-M) and Lehrstuhl für Biologische Chemie, Technische Universität München, 85354 Freising (Weihenstephan), Germany skerra@tum.de.
Technical University of Munich · DEUniversitätsklinikum des Saarlandes · DECenter for Integrated Protein Science Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyloid beta (Aβ) peptides, in particular Aβ42 and Aβ40, exert neurotoxic effects and their overproduction leads to amyloid deposits in the brain, thus constituting an important biomolecular target for treatments of Alzheimer's disease (AD). We describe the engineering of cognate Anticalins as a novel type of neutralizing protein reagent based on the human lipocalin scaffold. Phage display selection from a genetic random library comprising variants of the human lipocalin 2 (Lcn2) with mutations targeted at 20 exposed amino acid positions in the four loops that form the natural binding site was performed using both recombinant and synthetic target peptides and resulted in three different Anticalins. Biochemical characterization of the purified proteins produced by periplasmic secretion in Escherichia coli revealed high folding stability in a monomeric state, with Tm values ranging from 53.4°C to 74.5°C, as well as high affinities for Aβ40, between 95 pM and 563 pM, as measured by real-time surface plasmon resonance analysis. The central linear VFFAED epitope within the Aβ sequence was mapped using a synthetic peptide array on membranes and was shared by all three Anticalins, despite up to 13 mutual amino acid differences in their binding sites. All Anticalins had the ability-with varying extent-to inhibit Aβ aggregation in vitro according to the thioflavin-T fluorescence assay and, furthermore, they abolished Aβ42-mediated toxicity in neuronal cell culture. Thus, these Anticalins provide not only useful protein reagents to study the molecular pathology of AD but they also show potential as alternative drug candidates compared with antibodies.

Indexed as

Alzheimer DiseaseAmino Acid SequenceAmyloid beta-PeptidesBinding SitesHumansLipocalinsMolecular Sequence DataPeptide LibraryProtein BindingProtein ConformationProtein EngineeringAmyloid beta-PeptidesLipocalinsPeptide LibraryAβ peptidelipocalinneurodegenerationprotein engineering

Identifiers

PMID27029347
PMCPMC4888463
OpenAlexW2327228063

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.