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Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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Kinetic Screening of Nuclease Activity using Nucleic Acid Probes
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Convertible and conformationally constrained nucleic acids (C2NAs).

Jean-Marc Escudier1, Corinne Payrastre1, Béatrice Gerland1

  • 1Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, UMR CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France. escudier@chimie.ups-tlse.fr.

Organic & Biomolecular Chemistry
|June 19, 2019
PubMed
Summary

We developed Convertible and Constrained Nucleic Acids (C2NAs) to control DNA structure. This innovation allows for increased DNA duplex stability or hairpin formation, with potential for new functionalization via click chemistry.

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Area of Science:

  • Chemical Biology
  • Nucleic Acid Chemistry
  • Biotechnology

Background:

  • DNA structural flexibility is crucial for biological function.
  • Controlling DNA conformation is key for therapeutic and diagnostic applications.
  • Existing nucleic acid modifications have limitations in versatility and stability.

Purpose of the Study:

  • To introduce a novel class of nucleic acids, Convertible and Constrained Nucleic Acids (C2NAs).
  • To demonstrate the ability of C2NAs to modulate DNA structural properties.
  • To enable facile functionalization of nucleic acids using click chemistry.

Main Methods:

  • Synthesis of a stereocontrolled N-propargyl dioxo-1,3,2-oxaza-phosphorinane internucleotidic linkage.
  • Utilizing the linkage to control torsional angles (α and β) in nucleic acids.
  • Employing copper-catalyzed Huisgen's cycloaddition (CuAAC click chemistry) for functionalization.

Main Results:

  • C2NAs can adopt canonical (g-, t) or non-canonical (g+, t) torsional angles.
  • The (g-, t) conformation enhances DNA duplex stability.
  • The (g+, t) conformation stabilizes hairpin structures within nucleic acid loops.
  • Click chemistry allows for site-specific introduction of diverse functionalities.

Conclusions:

  • C2NAs offer unprecedented control over nucleic acid conformation and stability.
  • The developed linkage provides a versatile platform for nucleic acid engineering.
  • C2NAs hold promise for applications in DNA-based technologies and therapeutics.