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Activity-Based Probes for 15-Lipoxygenase-1.

Nikolaos Eleftheriadis1, Stephanie A Thee1, Martijn R H Zwinderman1

  • 1Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.

Angewandte Chemie (International Ed. in English)
|September 10, 2016
PubMed
Summary

Researchers developed a novel activity-based probe for human 15-lipoxygenase-1 (15-LOX-1). This probe enables efficient labeling of 15-LOX-1 in various biological samples for drug discovery.

Keywords:
Heck reactionactivity-based probesenzyme kineticsenzymesirreversible inhibition

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Area of Science:

  • Biochemistry
  • Enzymology
  • Drug Discovery

Background:

  • Human 15-lipoxygenase-1 (15-LOX-1) is implicated in inflammatory lung diseases (asthma, COPD, chronic bronchitis) and CNS diseases (Alzheimer's, Parkinson's, stroke).
  • Activity-based probes are crucial for further understanding 15-LOX-1's role and facilitating drug discovery.

Purpose of the Study:

  • To develop an efficient activity-based probe for human 15-lipoxygenase-1 (15-LOX-1).
  • To enable activity-based labeling of 15-LOX-1 in complex biological samples for research and drug development.

Main Methods:

  • Designed activity-based probes mimicking the natural substrate of 15-LOX-1.
  • Incorporated a terminal alkene for bioorthogonal linkage via oxidative Heck reaction.
  • Demonstrated efficient activity-based labeling of recombinant 15-LOX-1, cell lysates, and tissue samples.

Main Results:

  • Successfully developed a novel activity-based probe for human 15-LOX-1.
  • Achieved efficient and specific labeling of 15-LOX-1 in various biological contexts.
  • The probe utilizes a terminal alkene and oxidative Heck reaction for functionalization.

Conclusions:

  • The developed activity-based probe facilitates the investigation and identification of 15-LOX-1 in complex biological samples.
  • This advancement opens new avenues for drug discovery targeting 15-LOX-1 related diseases.