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Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2

Overview of attention for article published in Chemistry - A European Journal, May 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (83rd percentile)
  • High Attention Score compared to outputs of the same age and source (88th percentile)

Mentioned by

news
1 news outlet
twitter
1 tweeter

Citations

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13 Dimensions

Readers on

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21 Mendeley
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Title
Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2
Published in
Chemistry - A European Journal, May 2016
DOI 10.1002/chem.201600206
Pubmed ID
Authors

Daniela Häußler, Martin Mangold, Norbert Furtmann, Annett Braune, Michael Blaut, Jürgen Bajorath, Marit Stirnberg, Michael Gütschow

Abstract

Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and β-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Five active compounds (41-45) were identified and characterized kinetically as irreversible inhibitors of matriptase-2. In addition to a phosphonate warhead, these dipeptides possess two benzguanidine moieties as arginine mimetics to provide affinity for matriptase-2 by binding to the S1 and S3/S4 subpockets, respectively. This binding mode was strongly supported by covalent docking analysis. Compounds 41-45 were obtained as mixtures of two diastereomers and were therefore separated into the single epimers. Compound 45 A, with S configuration at the N-terminal amino acid and R configuration at the phosphonate carbon atom, was the most potent matriptase-2 inactivator with a rate constant of inactivation of 2790 m(-1)  s(-1) and abolished the activity of membrane-bound matriptase-2 on the surface of intact cells. Based on the chemotyp of phosphono bisbenzguanidines, the design and synthesis of a fluorescent probe (51 A) by insertion of a coumarin label is described. The in-gel fluorescence detection of matriptase-2 was demonstrated by applying 51 A as the first activity-based probe for this enzyme.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 19%
Researcher 3 14%
Student > Master 2 10%
Other 1 5%
Student > Bachelor 1 5%
Other 4 19%
Unknown 6 29%
Readers by discipline Count As %
Chemistry 7 33%
Pharmacology, Toxicology and Pharmaceutical Science 3 14%
Biochemistry, Genetics and Molecular Biology 2 10%
Agricultural and Biological Sciences 1 5%
Unknown 8 38%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 June 2016.
All research outputs
#1,369,864
of 12,183,333 outputs
Outputs from Chemistry - A European Journal
#756
of 11,921 outputs
Outputs of similar age
#45,963
of 278,102 outputs
Outputs of similar age from Chemistry - A European Journal
#45
of 485 outputs
Altmetric has tracked 12,183,333 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,921 research outputs from this source. They receive a mean Attention Score of 3.3. This one has done particularly well, scoring higher than 92% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 278,102 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 83% of its contemporaries.
We're also able to compare this research output to 485 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.