Evidence map›Paper›PMID 41287382›Full record

ArticleAngewandte Chemie (International ed. in English)2026

Covalent Activation of the C-type Lectin DC-SIGN.

Jonathan Lefèbre, Maurice Besch, Noémi Csorba, Kristóf Garami, Zoltán Orgován, Gitta Schlosser, Iris Bermejo, Péter Ábrányi-Balogh, György M Keserű, Christoph Rademacher

Abstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Synthetic Ligands of Myeloid C-Type Lectin Receptors.Chembiochem : a European journal of chemical biology · 2026
    Review
  2. Article
  3. Article
  4. Covalent Activation of the C-type Lectin DC-SIGN.Angewandte Chemie (International ed. in English) · 2026
    Article
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

10 authors.

Jonathan LefèbreDepartment of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, 1090, Austria.ORCID 0000-0001-8505-2181
Maurice BeschDepartment of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, 1090, Austria.ORCID 0000-0001-9242-0261
Noémi CsorbaMedicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt 2, Budapest, H-1117, Hungary.ORCID 0009-0007-5711-450X
Kristóf GaramiMedicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt 2, Budapest, H-1117, Hungary.ORCID 0009-0003-8208-012X
Zoltán OrgovánMedicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt 2, Budapest, H-1117, Hungary.ORCID 0000-0002-8002-3047
Gitta SchlosserMTA-ELTE Lendület Ion Mobility Mass Spectrometry Research Group, Institute of Chemistry, Eötvös Loránd University, Egyetem tér 1-3, Budapest, H-1053, Hungary.ORCID 0000-0002-7637-7133
Iris BermejoDepartment of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, 1090, Austria.ORCID 0000-0001-8864-4852
Péter Ábrányi-BaloghMedicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt 2, Budapest, H-1117, Hungary.ORCID 0000-0002-9284-5160
György M KeserűMedicinal Chemistry Research Group, HUN-REN Research Centre for Natural Sciences, Magyar tudósok krt 2, Budapest, H-1117, Hungary.ORCID 0000-0003-1039-7809
Christoph RademacherDepartment of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, Vienna, 1090, Austria.ORCID 0000-0001-7082-7239

Funding

Doctoral Excellence Fellowship Programme DCEP-25-1-BME-53European Commission for a Marie-Skłodowska Curie Fellowship 895202Marie Skłodowska Curie 956314National Laboratory for Drug Research and Development (PharmaLab) RRF-2.3.1-21-2022-00015National Research Fund, Luxembourg, AFR 17929849
6 · The paper itself

Abstract

Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a C-type lectin receptor expressed on antigen-presenting cells, crucial for pathogen recognition and immune modulation. The shallow and polar carbohydrate binding site of DC-SIGN presents challenges for ligand design. Here, we explored covalent modification targeting specific lysine residues as a novel strategy to modulate DC-SIGN function. Screening a lysine-targeted electrophilic fragment library using orthogonal functional assays identified two potent activators. Structural analyses via NMR spectroscopy, mass spectrometry and computational modeling confirmed structural perturbations of the carbohydrate recognition domain (CRD) and revealed distinct mechanisms of activation. While both activators significantly enhanced DC-SIGN's affinity for monosaccharide ligands, one compound induced oligomerization via covalent coupling and non-covalent secondary site interactions, whereas the other selectively modified lysine K373 directly within the primary carbohydrate binding site. These findings demonstrate the potential of lysine-targeted covalent compounds as a novel therapeutic strategy for modulating DC-SIGN function and potentially C-type lectins in general.

Indexed as

Cell Adhesion MoleculesLectins, C-TypeReceptors, Cell SurfaceBinding SitesHumansLigandsLysineCell Adhesion MoleculesLectins, C-TypeLigandsLysineReceptors, Cell SurfaceCovalent inhibitionDC‐SIGNFragment‐based drug designGlycobiologyProtein activation

Identifiers

PMID41287382
PMCPMC12811664

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.