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Related Experiment Videos

Boron-containing aptamers to ATP.

Susan M Lato1, Nicole D S Ozerova, Kaizhang He

  • 1Department of Chemistry, Indiana University, 800 East Kirkwood, Bloomington, IN 47405-7102, USA.

Nucleic Acids Research
|March 9, 2002
PubMed
Summary

Boron neutron capture therapy requires specific delivery agents. Researchers found that boronated nucleotides are compatible with aptamer selection processes, enabling the development of boronated aptamers for cancer treatment.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Biotechnology

Background:

  • Boron neutron capture therapy (BNCT) is an experimental cancer treatment.
  • Highly specific delivery agents are needed for BNCT.
  • Nucleic acid aptamers are known for their specific molecular targeting capabilities.

Purpose of the Study:

  • To investigate the impact of boronated nucleotide analogs on RNA function.
  • To assess the compatibility of boronated nucleotides within the SELEX process.
  • To explore the potential of creating boronated aptamers for BNCT.

Main Methods:

  • Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was employed.
  • Boronated nucleotide analogs, guanosine 5'-(alpha-P-borano) triphosphate (bG) and uridine 5'-(alpha-P-borano) triphosphate (bU), were substituted for their natural counterparts (GTP and UTP).

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  • Aptamer selections were performed using C8-linked ATP agarose as the target.
  • Main Results:

    • Substitution of bG or bU diminished or eliminated target recognition in some known aptamers.
    • ATP-binding aptamers with a zeta-fold structure were inactivated by bG substitution but only moderately affected by bU.
    • SELEX selections with bU yielded some zeta-fold aptamers, while bG selections did not.
    • Non-zeta aptamers from both bU and bG populations tolerated and often required the borano substitution.
    • The requirement for bU or bG was specific, with no cross-compatibility.

    Conclusions:

    • Boronated nucleotides (bG and bU) are fully compatible with the SELEX process.
    • These analogs can be used to generate boronated aptamers.
    • Boronated aptamers hold promise as therapeutic agents for BNCT.