Evidence map›Paper›PMID 35351585›Full record

ArticleBioorganic & medicinal chemistry letters2022

Exploration of inhibitors of the bacterial LexA repressor-protease.

Ana Victoria Cheng Jaramillo, Michael B Cory, Allen Li, Rahul M Kohli, William M Wuest

Abstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Base excision repair inFrontiers in microbiology · 2026
    Review
  2. Article
  3. mLife · 2024
    Review
  4. Integration of molecular modelling andFrontiers in cellular and infection microbiology · 2023
    Article
  5. 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

5 authors.

Ana Victoria Cheng JaramilloDepartment of Chemistry, Emory University, Atlanta, GA, USA.
Michael B CoryDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Allen LiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rahul M KohliDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rkohli@pennmedicine.upenn.edu.
William M WuestDepartment of Chemistry, Emory University, Atlanta, GA, USA. Electronic address: wwuest@emory.edu.

Funding

ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
Natural Product-Inspired Approaches Toward The Development Of Antivirulence And Species-Specific InhibitorsR35GM119426 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI William M Wuest · 2016 to 2026
$4.8M
Training in Microbial Pathogenesis and GenomicsT32AI141393 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI GOULIAN, MARK D, ZHU, JUN · 2019 to 2023
$1.3M
The Molecular Basis for the Bacterial SOS SignalR01GM127593 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU, PETERSSON, ERNEST JAMES · 2018 to 2021
$1.2M
Inhibition of the Bacterial LexA Repressor-Protease to Halt SOS Response-Mediated Resistance and Biofilm FormationF31AI152459 · NIAID · EMORY UNIVERSITY · PI CHENG, ANA V · 2020 to 2021
$82k
NIAID NIH HHS F31 AI152459NIAID NIH HHS T32 AI141393NIGMS NIH HHS R01 GM127593NIGMS NIH HHS R01 GM129325NIGMS NIH HHS R35 GM119426
6 · The paper itself

Abstract

Resistant and tolerant bacterial infections lead to billions in healthcare costs and cause hundreds of thousands of deaths each year. The bulk of current antibiotic research efforts focus on molecules which, although novel, are not immune from acquired resistance and seldomly affect tolerant populations. The bacterial SOS response has been implicated in several resistance and tolerance mechanisms, making it an attractive antibiotic target. Using small molecule inhibitors targeting a key step in the deployment of the SOS response, our approach focused on preventing the deployment of mechanisms such as biofilm formation, horizontal gene transfer, and error-prone DNA repair. Herein we report the synthesis and testing of analogs of a triazole-containing tricyclic inhibitor of LexA proteolysis, the key event in the SOS response. Our results hint that our inhibitor's may function by adopting a β-hairpin conformation, reminiscent of the native cleavage loop of LexA.

Indexed as

Peptide HydrolasesSOS Response, GeneticsAnti-Bacterial AgentsBacteriaBacterial ProteinsGene Expression Regulation, BacterialSerine EndopeptidasesAnti-Bacterial AgentsBacterial ProteinsPeptide HydrolasesSerine EndopeptidasesAntibiotic resistanceDNA damageSOS responseStress responseTolerance

Identifiers

PMID35351585
PMCPMC9071788

What OpenQuestion holds

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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.