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Mechanism-based candidate inhibitors of uridine diphosphate galactopyranose mutase (UGM)

Yasaman Mahdavi-Amiri1, Sankar Mohan1, Silvia Borrelli1

  • 1Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.

Carbohydrate Research
|November 24, 2015
PubMed

Insights

Researchers synthesized novel sulfonium and selenonium ions to mimic the transition state of the Uridine diphosphate-galactopyranose mutase (UGM) enzyme. These compounds showed moderate inhibition of UGM activity, offering potential for new therapeutic strategies against pathogens.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Microbiology

Background:

  • Uridine diphosphate-galactopyranose mutase (UGM) is crucial for synthesizing the mycobacterial cell wall.
  • UGM interconverts UDP-galactopyranose (UDP-Galp) and UDP-galactofuranose (UDP-Galf).
  • UDP-Galf is essential for the galactofuranose polymer component of the mycobacterium cell wall.

Purpose of the Study:

  • To design and synthesize novel transition state mimics for UGM.
  • To investigate the inhibitory potential of these mimics against UGM activity.

Main Methods:

  • Synthesis of sulfonium and selenonium ions with polyhydroxylated side chains.
  • Design of compounds to mimic the proposed galactopyranosyl cation-like transition state.
  • HPLC-based UGM inhibition assay to quantify enzyme activity.

Main Results:

  • Novel sulfonium and selenonium ions were successfully synthesized.
  • The synthesized compounds acted as transition state mimics for UGM.
  • Compounds inhibited approximately 25% of UGM activity at 500 µM concentration.

Conclusions:

  • The synthesized compounds demonstrate potential as UGM inhibitors.
  • These findings contribute to the development of novel therapeutic agents targeting mycobacterial infections.
  • Further optimization may lead to more potent UGM inhibitors.
Keywords:
Enzyme inhibitorsMycobacterium tuberculosisSynthesisTransition-state analoguesUDP-galactopyranose mutaseUGM

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