Evidence map›Paper›PMID 31445072›Full record

ArticleBiochimie2019

Modulating DNA by polyamides to regulate transcription factor PU.1-DNA binding interactions.

Beibei Liu, James K Bashkin, Gregory M K Poon, Shuo Wang, Siming Wang, W David Wilson

Open access · greenAbstract read
In one paragraph

Article in Biochimie, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

6 authors at 2 institutions in 1 country.

Beibei LiuDepartment of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.
James K BashkinDepartment of Chemistry & Biochemistry, Center for Nanoscience, University of Missouri-St. Louis, St. Louis, MO, 63121, USA.
Gregory M K PoonDepartment of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.
Shuo WangDepartment of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.
Siming WangDepartment of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.
W David WilsonDepartment of Chemistry, Georgia State University, Atlanta, GA, 30303, USA. Electronic address: wdw@gsu.edu.
Georgia State University · USUniversity of Missouri–St. Louis · US

Funding

Heterocycle Cation Recognition of the DNA Minor Groove.R01AI064200 · NIAID · GEORGIA STATE UNIVERSITY · PI WILSON, W DAVID · 2005 to 2014
$3.4M
Molecular Design for Specific Recognition of Functional DNA SequencesR01GM111749 · NIGMS · GEORGIA STATE UNIVERSITY · PI WILSON, W DAVID · 2014 to 2021
$2.5M
Biophysics of Drug Interactions with Viral EpisomesR01AI083803 · NIAID · UNIVERSITY OF MISSOURI-ST. LOUIS · PI BASHKIN, JAMES K. · 2010 to 2014
$1.8M
Direct chemical control of the hematopoietic master transcription factor PU.1R01HL155178 · NHLBI · GEORGIA STATE UNIVERSITY · PI POON, GREGORY MAN KAI · 2021 to 2023
$1.2M
NHLBI NIH HHS R01 HL155178NIAID NIH HHS R01 AI064200NIAID NIH HHS R01 AI083803NIGMS NIH HHS R01 GM111749
6 · The paper itself

Abstract

Hairpin polyamides are synthetic small molecules that bind DNA minor groove sequence-selectively and, in many sequences, induce widening of the minor groove and compression of the major groove. The structural distortion of DNA caused by polyamides has enhanced our understanding of the regulation of DNA-binding proteins via polyamides. Polyamides have DNA binding affinities that are comparable to those proteins, therefore, can potentially be used as therapeutic agents to treat diseases caused by aberrant gene expression. In fact, many diseases are characterized by over- or under-expressed genes. PU.1 is a transcription factor that regulates many immune system genes. Aberrant expression of PU.1 has been associated with the development of acute myeloid leukemia (AML). We have, therefore, designed and synthesized ten hairpin polyamides to investigate their capacity in controlling the PU.1-DNA interaction. Our results showed that nine of the polyamides disrupt PU.1-DNA binding and the inhibition capacity strongly correlates with binding affinity. One molecule, FH1024, was observed forming a FH1024-PU.1-DNA ternary complex instead of inhibiting PU.1-DNA binding. This is the first report of a small molecule that is potentially a weak agonist that recruits PU.1 to DNA. This finding sheds light on the design of polyamides that exhibit novel regulatory mechanisms on protein-DNA binding.

Indexed as

AnimalsBinding SitesDNAHumansMiceNylonsProtein BindingProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-ActivatorsDNANylonsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-ActivatorsETS familyHairpin polyamidePU.1Transcription factor inhibitionβ-alanine

Identifiers

PMID31445072
PMCPMC6883780
OpenAlexW2969845038

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.