Evidence map›Paper›PMID 27478158›Full record

ArticleCell chemical biology2016

Counter Selection Substrate Library Strategy for Developing Specific Protease Substrates and Probes.

Marcin Poreba, Rigmor Solberg, Wioletta Rut, Ngoc Nguyen Lunde, Paulina Kasperkiewicz, Scott J Snipas, Marko Mihelic, Dusan Turk, Boris Turk, Guy S Salvesen and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cell chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
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  11. Catch-enrich-release approach for amine-containing natural products.Chemical communications (Cambridge, England) · 2022
    Article
  12. Host protease activity classifies pneumonia etiology.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  13. Re-emerging Aspartic Protease Targets: ExaminingJournal of medicinal chemistry · 2021
    Article
  14. Review
  15. Article
  16. Article
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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

11 authors at 4 institutions in 4 countries.

Marcin PorebaDepartment of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb.Wyspianskiego 27, 50-370 Wroclaw, Poland; Program in Cell Death and Survival Networks, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: marcin.poreba@pwr.edu.pl.
Rigmor SolbergProgram in Cell Death and Survival Networks, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, 0316 Oslo, Norway. Electronic address: rigmor.solberg@farmasi.uio.no.
Wioletta RutDepartment of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb.Wyspianskiego 27, 50-370 Wroclaw, Poland.
Ngoc Nguyen LundeDepartment of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, 0316 Oslo, Norway.
Paulina KasperkiewiczDepartment of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb.Wyspianskiego 27, 50-370 Wroclaw, Poland.
Scott J SnipasProgram in Cell Death and Survival Networks, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Marko MihelicDepartment of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia.
Dusan TurkDepartment of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia.
Boris TurkDepartment of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia.
Guy S SalvesenProgram in Cell Death and Survival Networks, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Marcin DragDepartment of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb.Wyspianskiego 27, 50-370 Wroclaw, Poland. Electronic address: marcin.drag@pwr.edu.pl.
Wrocław University of Science and Technology · PLJožef Stefan Institute · SISanford Burnham Prebys Medical Discovery Institute · USUniversity of Oslo · NO

Funding

Survival Mechanisms for Apoptotic CaspaseR01GM099040 · NIGMS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI SALVESEN, GUY S. · 2012 to 2020
$3.8M
NIGMS NIH HHS R01 GM099040
6 · The paper itself

Abstract

Legumain (AEP) is a lysosomal cysteine protease that was first characterized in leguminous seeds and later discovered in higher eukaryotes. AEP upregulation is linked to a number of diseases including inflammation, arteriosclerosis, and tumorigenesis. Thus this protease is an excellent molecular target for the development of new chemical markers. We deployed a hybrid combinatorial substrate library (HyCoSuL) approach to obtain P1-Asp fluorogenic substrates and biotin-labeled inhibitors that targeted legumain. Since this approach led to probes that were also recognized by caspases, we introduced a Counter Selection Substrate Library (CoSeSuL) approach that biases the peptidic scaffold against caspases, thus delivering highly selective legumain probes. The selectivity of these tools was validated using M38L and HEK293 cells. We also propose that the CoSeSuL methodology can be considered as a general principle in the design of selective probes for other protease families where selectivity is difficult to achieve by conventional sequence-based profiling.

Indexed as

Combinatorial Chemistry TechniquesAsparaginyl EndopeptidaseCell LineCysteine EndopeptidasesEnzyme InhibitorsHumansHydrogen-Ion ConcentrationMolecular ConformationMolecular ProbesSubstrate SpecificityAsparaginyl EndopeptidaseCysteine EndopeptidasesEnzyme InhibitorsMolecular Probes

Identifiers

PMID27478158
PMCPMC5939596
OpenAlexW2500366071

What OpenQuestion holds

Textmetadata
LicenceTDM
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.