Evidence map›Paper›PMID 34584954›Full record

ArticleACS central science2021

Activity-Based Hydrazine Probes for Protein Profiling of Electrophilic Functionality in Therapeutic Targets.

Zongtao Lin, Xie Wang, Katelyn A Bustin, Kyosuke Shishikura, Nate R McKnight, Lin He, Radu M Suciu, Kai Hu, Xian Han, Mina Ahmadi and 3 more

Abstract read
In one paragraph

Article in ACS central science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Flipping the polarity switch.Nature chemical biology · 2023
    Article
  16. Article
  17. Article
  18. Characterizing metabolic drivers ofFrontiers in pharmacology · 2023
    Article
  19. Article
  20. Advances in covalent drug discovery.Nature reviews. Drug discovery · 2022
    Review
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

13 authors.

Zongtao LinDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Xie WangDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID https://orcid.org/0000-0002-7292-5550
Katelyn A BustinDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID https://orcid.org/0000-0001-8933-9825
Kyosuke ShishikuraDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Nate R McKnightDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Lin HeZenagem, LLC, Fountain Valley, California 92708, United States.ORCID https://orcid.org/0000-0003-4945-2107
Radu M SuciuDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Kai HuDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, United States.
Xian HanDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, United States.
Mina AhmadiDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Erika J OlsonDepartment of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
William H ParsonsDepartment of Chemistry and Biochemistry, Oberlin College, Oberlin, Ohio 44074, United States.ORCID https://orcid.org/0000-0001-6065-2340
Megan L MatthewsDepartment of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.ORCID https://orcid.org/0000-0003-1178-4616

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Most known probes for activity-based protein profiling (ABPP) use electrophilic groups that tag a single type of nucleophilic amino acid to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electrophilic enzyme cofactors, transient intermediates, and labile regulatory modifications, but ABPP probes for such species are underdeveloped. Here, we describe a versatile class of probes for this less charted hemisphere of the proteome. The use of an electron-rich hydrazine as the common chemical modifier enables covalent targeting of multiple, pharmacologically important classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment occurs by both polar and radicaloid mechanisms, can be blocked by molecules that occupy the active sites, and depends on the proper poise of the active site for turnover. These traits will enable the probes to be used to identify specific inhibitors of individual members of these multiple enzyme classes, making them uniquely versatile among known ABPP probes.

Identifiers

PMID34584954
PMCPMC8461768

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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.