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Related Experiment Videos

Calcium-dependent oligonucleotide antagonists specific for L-selectin

D O'Connell1, A Koenig, S Jennings

  • 1NeXstar Pharmaceuticals Inc., Boulder, CO 80301, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 11, 1996
PubMed
Summary

Researchers developed novel aptamers that effectively block L-selectin, a key molecule in inflammatory responses. These high-affinity aptamers offer a promising, specific therapeutic strategy for inflammatory and postischemic conditions.

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Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • Selectins are calcium-dependent C-type lectins crucial for cell-cell interactions in the vascular system.
  • Selectin blockade is a potential therapeutic strategy for inflammatory and postischemic diseases.
  • Current ligand mimetics have low affinity and lack specificity across different selectins.

Purpose of the Study:

  • To develop high-affinity, specific antagonists for L-selectin using the SELEX process.
  • To overcome the limitations of existing oligosaccharide-based selectin blockers.

Main Methods:

  • Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was employed.
  • Nuclease-stabilized randomized oligonucleotides were selected against recombinant L-selectin.

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  • Binding affinities and specificities of the selected aptamers were evaluated.

    • Main Results:

    • SELEX yielded calcium-dependent aptamer antagonists with ~10^5 higher affinity than sialyl LewisX.
    • The aptamers exhibited high specificity for L-selectin, with minimal cross-reactivity to E- or P-selectin.
    • These aptamers demonstrated calcium-dependent binding to native L-selectin on lymphocytes and blocked L-selectin-mediated adhesion.

    Conclusions:

    • Novel aptamers derived from SELEX are potent and specific L-selectin antagonists.
    • These aptamers represent a significant advancement over conventional ligand mimetics for therapeutic applications.
    • The developed aptamers show promise for treating inflammatory and postischemic conditions by blocking L-selectin pathways.