Modifikace kostry oligonukleotidů

Backbone modifications alter the fundamental sugar–phosphate structure of an oligonucleotide.
They are used to enhance stability, nuclease resistance, and binding affinity, making oligos suitable for demanding biological and therapeutic applications.

Backbone modifications refer to chemical changes that affect the sugar–phosphate backbone of an oligonucleotide. These modifications alter the fundamental structure of the oligo rather than modifying individual bases or attaching external labels.

Modifications classified as Backbone Modifications

The following types of modifications are considered backbone modifications because they directly alter either the phosphate linkage or the sugar moiety of the nucleotide backbone:

• Phosphorothioate linkages
  Replacement of a non-bridging oxygen atom in the phosphate group with sulfur, leading to enhanced nuclease resistance and improved in vivo stability.
• RNA backbone (rA, rC, rG, rU)
  Substitution of deoxyribose with ribose, changing the backbone chemistry and structural conformation of the oligonucleotide.
• Sugar-modified RNA backbones
  • 2′-O-Methyl RNA (2′-OMe RNA)
  • 2′-Fluoro RNA (2′-F RNA)
    These modifications alter the 2′ position of the ribose sugar, increasing chemical and enzymatic stability and improving binding affinity.
• Locked Nucleic Acids (LNA) / Bridged Nucleic Acids (BNA)
  Chemical locking of the ribose ring into a fixed conformation, resulting in a rigid backbone with strongly enhanced hybridization affinity and stability.

What is NOT considered a Backbone Modification

Backbone modifications affect the entire oligonucleotide framework and should not be confused with base analogs or internal labels, which modify only individual nucleotides or add functional groups.

• Base analogs (e.g. 5‑methyl‑dC, 7‑deaza‑dA, inosine)
• Fluorophores, quenchers, biotin, reactive groups
• Spacers and blocking groups
• Degenerate or mixed bases

These modifications affect bases or add functional labels but do not alter the sugar–phosphate backbone itself.

Table‑Style Definition for Customer Documentation

 Radovan Haluza