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Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
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Using Modified Synthetic Oligonucleotides to Assay Nucleic Acid-Metabolizing Enzymes
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Making oligonucleotide conjugates and breaking oligonucleotides.

S Milton1, M Murtola, J Sandbrink

  • 1Department of Biosciences & Nutrition, Novum, Karolinska Institutet, S-14157 Huddinge, Sweden.

Nucleic Acids Symposium Series (2004)
|November 22, 2007
PubMed
Summary

We synthesized novel oligonucleotide analogues and conjugates, including peptide-oligonucleotide and RNA-cleaving types. These advanced materials show promise for applications in nucleic acid modification and therapeutic development.

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Area of Science:

  • Medicinal Chemistry
  • Organic Chemistry
  • Biochemistry

Background:

  • Oligonucleotide analogues are crucial in developing new therapeutics.
  • Conjugation strategies enhance oligonucleotide properties and functionalities.
  • Understanding interactions like Watson-Crick is key for nucleic acid applications.

Purpose of the Study:

  • To synthesize and characterize novel oligonucleotide analogues and conjugates.
  • To explore the properties of 2'-carbamoylmethyl derivatives and peptide-oligonucleotide conjugates.
  • To investigate conjugates combining different binding modes and RNA-cleaving functionalities.

Main Methods:

  • Chemical synthesis of modified oligonucleotides.
  • Preparation of peptide-oligonucleotide conjugates.
  • Design and synthesis of conjugates with RNA-cleaving moieties.
  • Characterization of synthesized compounds.

Main Results:

  • Successful synthesis of 2'-carbamoylmethyl oligonucleotide analogues.
  • Creation of peptide-oligonucleotide conjugates with potential therapeutic applications.
  • Development of conjugates facilitating both Watson-Crick and non-Watson-Crick interactions.
  • Demonstration of RNA cleavage by novel artificial nucleases.

Conclusions:

  • Novel oligonucleotide analogues and conjugates were successfully synthesized.
  • The developed conjugates offer versatile platforms for nucleic acid research and drug delivery.
  • Artificial nucleases show potential for targeted RNA cleavage applications.