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Structural analysis of nucleic acid aptamers

D J Patel1

  • 1Cellular Biochemistry & Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. pateld@mskcc.org

Current Opinion in Chemical Biology
|June 1, 1997
PubMed
Summary

Recent studies reveal the structures of ligand-nucleic acid aptamer complexes. These findings offer insights into molecular recognition and adaptive binding, aiding structure-based drug design for therapeutic interventions.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Structural Biology
  • Drug Discovery

Background:

  • Nucleic acid aptamers exhibit high specificity and affinity for various ligands.
  • Understanding the structural basis of ligand-aptamer interactions is crucial for therapeutic applications.

Purpose of the Study:

  • To elucidate the solution structures and hydrogen exchange characteristics of ligand-RNA and ligand-DNA aptamer complexes.
  • To gain insights into the principles of molecular recognition and adaptive binding in nucleic acid-ligand interactions.

Main Methods:

  • Solution structure determination using NMR spectroscopy.
  • Hydrogen-deuterium exchange mass spectrometry (HDX-MS) to study dynamics.

Main Results:

  • Detailed structures of diverse ligand-aptamer complexes (cofactors, amino acids, nucleotides, antibiotics, peptides) were solved.
  • Hydrogen exchange data provided insights into the dynamics and adaptive binding mechanisms.
  • Structural and dynamic studies revealed patterns in nucleic acid architecture and molecular recognition.

Conclusions:

  • The solved structures and dynamics provide a foundation for understanding aptamer-ligand recognition.
  • These findings support the development of structure-based drug design strategies for aptamer-based therapeutics.
  • The study highlights the diversity and adaptive nature of nucleic acid-ligand interactions.

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