Evidence map›Paper›PMID 41195166›Full record

ArticleRSC chemical biology2026

Nucleobase catalysts for the enzymatic activation of 8-oxoguanine DNA glycosylase 1.

Emily C Hank, Nicholas D D'Arcy-Evans, Emma Rose Scaletti, Carlos Benítez-Buelga, Olov Wallner, Florian Ortis, Kaixin Zhou, Liuzhen Meng, Alicia Del Prado, Patricia Calvo and 22 more

Abstract read
In one paragraph

Article in RSC chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

32 authors.

Emily C HankScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Nicholas D D'Arcy-EvansScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Emma Rose ScalettiDepartment of Biochemistry and Biophysics, Stockholm University Stockholm Sweden.
Carlos Benítez-BuelgaInstituto de Investigaciones Biomédicas Alberto Sols CSIC/UAM Madrid Spain.
Olov WallnerScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Florian OrtisScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Kaixin ZhouScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Liuzhen MengScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Alicia Del PradoCentro de Biología Molecular 'Severo Ochoa' (CSIC-UAM) Madrid Spain.ORCID https://orcid.org/0000-0002-5480-0367
Patricia CalvoCentro de Biología Molecular 'Severo Ochoa' (CSIC-UAM) Madrid Spain.
Ingrid AlmlöfScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Elisée WiitaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Karen NierlinScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Sara KošeninaDepartment of Biochemistry and Biophysics, Stockholm University Stockholm Sweden.
Andreas KrämerInstitute of Pharmaceutical Chemistry & Structural Genomics Consortium (SGC), Goethe University Frankfurt Germany.
Alice EddershawScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Mario KehlerScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Maeve LongScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Ann-Sofie JemthScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Holly DawsonScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Josephine StewartScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Adam DickeyScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Mikhael E AstorgaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Marek VargaScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Evert J HomanScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.ORCID https://orcid.org/0000-0002-9057-1848
Martin ScobieScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Stefan KnappInstitute of Pharmaceutical Chemistry & Structural Genomics Consortium (SGC), Goethe University Frankfurt Germany.ORCID https://orcid.org/0000-0001-5995-6494
Leandro SastreInstituto de Investigaciones Biomédicas Alberto Sols CSIC/UAM Madrid Spain.
Pål StenmarkDepartment of Biochemistry and Biophysics, Stockholm University Stockholm Sweden.
Miguel de VegaCentro de Biología Molecular 'Severo Ochoa' (CSIC-UAM) Madrid Spain.ORCID https://orcid.org/0000-0003-1285-7549
Thomas HelledayScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.
Maurice MichelScience for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet and Center for Molecular Medicine, Karolinska Institutet and Karolinska Hospital Stockholm Sweden maurice.michel@ki.se.ORCID https://orcid.org/0000-0003-3261-2493

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bifunctional DNA glycosylases employ an active site lysine or the N-terminus to form a Schiff base with an abasic (AP) site base excision repair intermediate. For 8-oxoguanine DNA glycosylase 1 (OGG1), cleaving this reversible structure is the rate-determining step in the initiation of 8-oxoguanine (8-oxoG) repair in DNA. Evolution has led OGG1 to use a product-assisted catalysis approach, where the excised 8-oxoG acts as a Brønsted base for cleavage of a Schiff base intermediate. However, the physicochemical properties of 8-oxoG significantly limit the inherent enzymatic turnover leading to a weak, cellularly absent, AP lyase activity. We hypothesized that chemical synthesis of purine analogues enables access to complex structures that are suitable as product-like catalysts. Herein, the nucleobase landscape is profiled for its potential to increase OGG1 Schiff base cleavage. 8-Substituted 6-thioguanines emerge as potent and selective scaffolds enabling OGG1 to cleave AP sites opposite any canonical nucleobase by β-elimination. This effectively broadens the enzymatic substrate scope of OGG1, shaping a complete, artificial AP-lyase function. In addition, a second class of compounds, 6-substituted pyrazolo-[3,4-

Identifiers

PMID41195166
PMCPMC12584757

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.