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Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution

R F Macaya1, P Schultze, F W Smith

  • 1Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.

Proceedings of the National Academy of Sciences of the United States of America
|April 15, 1993
PubMed
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This study used NMR to determine the structure of a thrombin-binding DNA aptamer. The aptamer forms a specific quadruplex structure, which is crucial for developing new DNA-based thrombin inhibitors.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Thrombin-binding DNA aptamers are a novel class of molecules that inhibit thrombin activity.
  • Aptamers are short DNA or RNA sequences that fold into specific three-dimensional structures to bind target molecules.
  • Understanding aptamer structure is key to optimizing their therapeutic potential.

Purpose of the Study:

  • To elucidate the solution conformation of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG).
  • To characterize the structural basis for aptamer-thrombin interaction.

Main Methods:

  • Two-dimensional proton nuclear magnetic resonance (1H NMR) spectroscopy was employed.
  • NMR data was used to determine the three-dimensional structure of the aptamer.

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Main Results:

  • The aptamer forms a unimolecular DNA quadruplex structure in solution.
  • This quadruplex consists of two G-quartets linked by TT and TGT loops.
  • A potential T.T base pair forms between the TT loops, stabilizing the structure.

Conclusions:

  • The thrombin-binding aptamer adopts a specific, folded quadruplex structure.
  • This structural information is vital for the rational design of oligonucleotide-based thrombin inhibitors.
  • The findings contribute to the development of novel anticoagulant therapies.