Discovery of a Reversible Sub-Picomolar Thrombin Inhibitor Using DCC.

Millicent Dockerill, Richard J Payne, Nicolas Winssinger

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. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

3 authors.

Millicent DockerillDepartment of Organic Chemistry, Faculty of Sciences, University of Geneva, Geneva, Switzerland.

Richard J PayneSchool of Chemistry, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-3618-9226

Nicolas WinssingerDepartment of Organic Chemistry, Faculty of Sciences, University of Geneva, Geneva, Switzerland.ORCID 0000-0003-1636-7766

Funding

Swiss National Science Foundation 200020_219316

6 · The paper itself

Abstract

Dynamic combinatorial chemistry (DCC) offers a powerful yet underutilized strategy for ligand discovery, largely limited by heterogeneous kinetic constraints in exchange reactions and analytical challenges. Here we report a peptide nucleic acid (PNA)-templated trivalent DCC platform that enables rapid, target-guided exploration of 125 000 assemblies to identify ultrahigh-affinity and reversible thrombin inhibitors. Short hybridization handles allow unbiased equilibration of a three-fragment library, and size-exclusion filtration combined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides a complete selection-readout cycle in under 1 h. From this library, thrombin amplifies synergistic fragment combinations engaging the active site and both exosites, yielding a trivalent inhibitor with apparent sub-picomolar affinity (K

Indexed as

AntithrombinsCombinatorial Chemistry TechniquesDrug DiscoveryPeptide Nucleic AcidsThrombinHumansSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationAntithrombinsPeptide Nucleic AcidsThrombinactive sitechemistrycombinatorial chemistryligandmass spectrometrymass spectrometry imagingnucleic acidpeptide nucleic acidthrombin

Identifiers

PMID42454810

DOI10.1002/anie.5778436

PMCPMC13573113

What OpenQuestion holds

Textmetadata

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Registered trials

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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.