Evidence map›Paper›PMID 26635020›Full record

ArticleAnalytical and bioanalytical chemistry2016

Identification of sirtuin 5 inhibitors by ultrafast microchip electrophoresis using nanoliter volume samples.

Erik D Guetschow, Surinder Kumar, David B Lombard, Robert T Kennedy

Abstract readEvaluation Study
In one paragraph

Article in Analytical and bioanalytical chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

20 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
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  5. Article
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  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology.Critical reviews in biochemistry and molecular biology · 2018
    Review
  14. Emerging Roles for SIRT5 in Metabolism and Cancer.Antioxidants & redox signaling · 2018
    Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. 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

4 authors at 1 institution in 1 country.

Erik D GuetschowDepartment of Chemistry, University of Michigan, 930 N University Ave, Ann Arbor, MI, 48109, USA.
Surinder KumarDepartment of Pathology, University of Michigan, 1301 Catherine St, Ann Arbor, MI, 48109, USA.
David B LombardDepartment of Pathology, University of Michigan, 1301 Catherine St, Ann Arbor, MI, 48109, USA.
Robert T KennedyDepartment of Chemistry, University of Michigan, 930 N University Ave, Ann Arbor, MI, 48109, USA. rtkenn@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Microfluidics in Biomedical Sciences Training ProgramT32EB005582 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FAN, XUDONG · 2005 to 2020
$3.9M
Regulation of one carbon metabolism and epigenetics by SIRT5R01GM101171 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOMBARD, DAVID BENNER · 2012 to 2021
$2.6M
High throughput mass spectrometry and electrophoresis assay systemsR01GM102236 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KENNEDY, ROBERT T · 2012 to 2015
$1.1M
NCATS NIH HHS UL1 TR000433NCATS NIH HHS UL1TR000433NIBIB NIH HHS T32 EB005582NIDDK NIH HHS P30 DK020572NIGMS NIH HHS R01 GM101171NIGMS NIH HHS R01GM101171NIGMS NIH HHS R01 GM102236NIGMS NIH HHS R01GM102236
6 · The paper itself

Abstract

Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that catalyzes removal of post-translational modifications, such as succinyl and malonyl moieties, on lysine residues. In light of SIRT5's roles in regulating metabolism, and its reported oncogenic functions, SIRT5 modulators would be valuable tools for basic biological research and perhaps clinically. Several fluorescence assays for sirtuin modulators have been developed; however, the use of fluorogenic substrates has the potential to cause false positive results due to interactions of engineered substrates with enzyme or test compounds. Therefore, development of high-throughput screening (HTS) assays based on other methods is valuable. In this study, we report the development of a SIRT5 assay using microchip electrophoresis (MCE) for identification of SIRT5 modulators. A novel SIRT5 substrate based on succinate dehydrogenase (SDH) was developed to allow rapid and efficient separation of substrate and product peptide. To achieve high throughput, samples were injected onto the microchip using a droplet-based scheme. By coupling this approach to existing HTS sample preparation workflows, 1408 samples were analyzed at 0.5 Hz in 46 min. Using a 250 ms separation time, eight MCE injections could be made from each sample generating >11,000 electropherograms during analysis. Of the 1280 chemicals tested, eight were identified as inhibiting SIRT5 activity by at least 70% and verified by dose-response analysis.

Indexed as

Electrophoresis, MicrochipEnzyme InhibitorsKineticsSirtuinsSubstrate SpecificityEnzyme InhibitorsSirtuinsDropletsElectrophoresisMicrofluidicsScreeningSirtuin

Identifiers

PMID26635020
PMCPMC4712073
OpenAlexW2186980337

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.