Evidence map›Paper›PMID 25901944›Full record

ArticleNature communications2015

Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer.

Laure Yatime, Christian Maasch, Kai Hoehlig, Sven Klussmann, Gregers R Andersen, Axel Vater

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Application of aptamers in regenerative medicine.Frontiers in bioengineering and biotechnology · 2022
    Pooled it
  2. Pooled it
  3. Aptamers in cancer therapy: Why has clinical translation lagged behind preclinical promise?Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
    Review
  4. Review
  5. Spiegelmer Aptamers: Innovative Approach in Breast Cancer.Breast cancer : basic and clinical research · 2026
    Review
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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 2 institutions in 2 countries.

Laure YatimeDepartment of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus, Denmark.
Christian MaaschNOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
Kai HoehligNOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.ORCID 0000000246384826
Sven KlussmannNOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.
Gregers R AndersenDepartment of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, DK-8000 Aarhus, Denmark.
Axel VaterNOXXON Pharma AG, Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany.ORCID 000000034166982X
Noxxon Pharma (Germany) · DEAarhus University · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the first crystallographic structures of an active Spiegelmer, NOX-D20, bound to its physiological targets, mouse C5a and C5a-desArg. The structures reveal a complex 3D architecture for the L-aptamer that wraps around C5a, including an intramolecular G-quadruplex stabilized by a central Ca(2+) ion. Functional validation of the observed L-aptamer:C5a binding mode through mutational studies also rationalizes the specificity of NOX-D20 for mouse and human C5a against macaque and rat C5a. Finally, our structural model provides the molecular basis for the Spiegelmer affinity improvement through positional L-ribonucleotide to L-deoxyribonucleotide exchanges and for its inhibition of the C5a:C5aR interaction.

Indexed as

AnaphylatoxinsAnimalsAptamers, NucleotideCalciumCell LineCell Migration AssaysComplement C5aComplement C5a, des-ArginineCrystallography, X-RayDNAEscherichia coliHumansMacacaMiceNucleic Acid ConformationRatsAnaphylatoxinsAptamers, NucleotideC5AR1 protein, humanCalciumComplement C5aComplement C5a, des-ArginineDNANOX-D20Receptor, Anaphylatoxin C5aRecombinant ProteinsRNA

Identifiers

PMID25901944
PMCPMC4423239
OpenAlexW1531021692

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.