Glycopolymer Binding to SIGNR1, A Mouse Orthologue of Human DC-SIGN - - PowerPoint PPT Presentation

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Glycopolymer Binding to SIGNR1, A Mouse Orthologue of Human DC-SIGN - - PowerPoint PPT Presentation

Feb 07, 2024 156 likes •318 views

Glycopolymer Binding to SIGNR1, A Mouse Orthologue of Human DC-SIGN M. Lougher Contents DC-SIGN Glycopolymers Why Use SIGNR1? Surface Plasmon Resonance Results Conclusions 2 DC-SIGN Membrane protein found in

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Glycopolymer Binding to SIGNR1, A Mouse Orthologue

  • f Human DC-SIGN
  • M. Lougher
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Contents

  • DC-SIGN
  • Glycopolymers
  • Why Use SIGNR1?
  • Surface Plasmon Resonance
  • Results
  • Conclusions

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DC-SIGN

  • Membrane protein found in dendritic cells and

some types of macrophages.

  • Receptor cells of this type traditionally bind to

pathogens and present them to T-cells for destruction.

  • DC-SIGN binds to HIV and presents that to T-

cells, but instead of being digested the HIV infects the T-cell.

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  • 1. H. Feinberg et al., J. Mol. Biol., 394, 613–620 (2009)

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DC-SIGN

  • C-type lectin; binds to mannose rich pathogens.
  • GP120 in HIV envelope has mannose groups.
  • Aim to design prophylactic treatment that binds to

the carbohydrate recognition domain (CRD) and prevents GP120 from binding.

  • One possible solution is glycopolymers.

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  • 1. H. Feinberg et al., J. Mol. Biol., 394, 613–620 (2009)

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Glycopolymers

  • Polymer chain with sugar groups attached.
  • Used 3 different shape polymers each bound with multiple

mannose groups.

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Straight Chain (DP60) 5 Arm 8 Arm

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Why Use SIGNR1?

  • Mouse orthologue of DC-SIGN.
  • Test to see if experiments on mice would be relevant to

research for human treatment.

  • Would allow research without using human tissue; much easier

to carry out.

  • Need to test to see if binding of glycopolymers

is comparable both in-vitro and in-vivo.

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Surface Plasmon Resonance

  • Method of detecting binding to a thin gold surface as refractive

index changes.

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  • 2. M. Cooper, Nature Reviews Drug Discovery 1, 515-528 (2002)

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Results

  • MAN DP60

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Results

  • MAN-8ARM

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Results

  • MAN-5ARM

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Results

  • Regeneration

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Results

  • Flow Cytometry

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Results

  • Cytotoxicity

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Summary

  • MAN DP60 shown to bind well to DC-SIGN and SIGNR1.
  • Further work needed for conclusive results of MAN-5ARM and

MAN-8ARM.

  • Demonstrated cytokines increase binding to cells.
  • Shown that polymers are not toxic to cells in concentrations

used.

  • Binding profiles similar for SIGNR1 and DC-SIGN; mouse

disease models can be used to develop human treatment.

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Acknowledgements

  • Thanks to:

– Dan Mitchell – Remzi Becer – Tariq Pathan – Rob Deller – Florence Hariton

  • Funded by:

– MOAC – EPSRC

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