Evidence map›Paper›PMID 30347143›Full record

ArticleJournal of the American Chemical Society2018

Design of a DNA-Programmed Plasminogen Activator.

Purba Mukherjee, Luke J Leman, John H Griffin, M Reza Ghadiri

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

13 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. DNA Strand Displacement Driven by Host-Guest Interactions.Journal of the American Chemical Society · 2022
    Article
  8. Applications of DNA-Functionalized Proteins.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Structural Biology and Protein Engineering of Thrombolytics.Computational and structural biotechnology journal · 2019
    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

4 authors at 1 institution in 1 country.

Purba MukherjeeDepartment of Chemistry , The Scripps Research Institute , La Jolla , California 92037 , United States.ORCID 0000-0001-9869-6509
Luke J LemanDepartment of Chemistry , The Scripps Research Institute , La Jolla , California 92037 , United States.ORCID 0000-0002-1879-5900
John H GriffinDepartment of Molecular Medicine , The Scripps Research Institute , La Jolla , California 92037 , United States.
M Reza GhadiriDepartment of Chemistry , The Scripps Research Institute , La Jolla , California 92037 , United States.
Scripps Research Institute · US

Funding

Scripps Translational Science InstituteUL1TR001114 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2013 to 2017
$24.0M
Regulation of Protein C PathwaysR01HL142975 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H, MOSNIER, LAURENT OLIVIER · 2018 to 2025
$7.3M
Human exomics genotyping-driven discovery and characterization of proteins related to clinical thrombosis, blood coagulation and thrombin generationR01HL133728 · NHLBI · SCRIPPS RESEARCH INSTITUTE, THE · PI GRIFFIN, JOHN H · 2016 to 2019
$1.9M
NCATS NIH HHS UL1 TR001114NHLBI NIH HHS R01 HL133728NHLBI NIH HHS R01 HL142975
6 · The paper itself

Abstract

Although the functional specificity and catalytic versatility of enzymes have been exploited in numerous settings, controlling the spatial and temporal activity of enzymes remains challenging. Here we describe an approach for programming the function of streptokinase (SK), a protein that is clinically used as a blood "clot buster" therapeutic. We show that the fibrinolytic activity resulting from the binding of SK to the plasma proenzyme plasminogen (Pg) can be effectively regulated (turned "OFF" and "ON") by installing an intrasteric regulatory feature using a DNA-linked protease inhibitor modification. We describe the design rationale, synthetic approach, and functional characterization of two generations of intrasterically regulated SK-Pg constructs and demonstrate dose-dependent and sequence-specific temporal control in fibrinolytic activity in response to short predesignated DNA inputs. The studies described establish the feasibility of a new enzyme-programming approach and serves as a step toward advancing a new generation of programmable enzyme therapeutics.

Indexed as

Drug DesignDNAHumansPlasminogen ActivatorsProtease InhibitorsStreptokinaseDNAPlasminogen ActivatorsProtease InhibitorsStreptokinase

Identifiers

PMID30347143
PMCPMC7115153
OpenAlexW2897207821

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.