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Backbone Modifications

LGC, Biosearch Technologies offers a wide range of high-quality amidites and reagents for modifying oligo backbones—all available in popular pack sizes and packaging formats, and most are available in bulk quantities.

Nucleoside phosphate backbone modifications are useful for increasing the stability of oligonucleotides duplexes and expanding the library of potential conjugates. Many oligo backbone modifications create unique binding capabilities and bolster sequence discrimination, making them useful for a variety of diagnostic and therapeutic applications such as SNP genotyping, antisense oligonucleotides, siRNA, and cell delivery.

We are constantly growing our portfolio of amidites and solid supports for incorporating oligo backbone modifications, and we listen to what our customers need. We now offer several locked nucleic acid (LNA) phosphoramidites and CPGs, as well as methyl and ethyl phosphoramidites.

Oligo backbone modification categories

Peptide nucleic acids (PNA)
Generate oligos with a neutral backbone that assists in binding DNA, RNA and double-stranded DNA. Synthesis resembles peptide synthesis. 
Locked nucleic acids (LNA)
Synthesise oligos that strongly and specifically bind to DNA, RNA and double-stranded DNA. LNA oligos are synthesised using conventional phosphoramidite chemistry.
Sulphurising reagent (EDITH)
Enable efficient and site-specific sulphurisation. This reagent is soluble in acetonitrile and stable in solution for several months.​​​​​​​
Within one reaction the backbone of the entire oligonucleotide is converted to the required form (e.g., thiophosphate-sugar backbone).
Alkyl phosphoramidites
Generate uncharged and nuclease-resistant oligonucleotide linkages— particularly useful for targeted cellular delivery of antisense therapeutic agents.
Methyl or ethyl phosphoramidites
Improve cell delivery with our expanded offering of methyl phosphoramidites.
Phosphorothioates (PS-oligos)
Replace non-bridging oxygen atoms with sulphur atoms to facilitate the attachment of site-specific reporter groups onto the DNA or RNA backbone or to create thioaptamers.

Properties of modified oligonucleotides

Chemistry  Increased affinity RNase H activity  Nuclease resistance
LNA Yes Yes (as chimera) Yes
DNA No Yes No
RNA No No No
PS-DNA No Yes Yes
PNA Yes No Yes

Examples of suitable applications for different backbone modifications

Backbone modification Applications
Alkyl phosphonamidites
  • Targeted cellular delivery of antisense therapeutic agents
Methyl or ethyl phosphoramidites
  • Incorporation into liposomes, inhibition of protein expression and cell growth in therapeutic applications
  • Synthesis of radiolabelled phosphorothioates
  • Preparation of internucleotide linkages that are not attainable by phosphoramidite chemistry
Locked nucleic acids (LNA)
  • Gene therapy
  • Synthetic siRNAs
  • qPCR probes
  • SNP genotyping
  • Allele-specific PCR
  • Decoy oligonucleotides
  • LNAzymes Specific cleavage of RNA
  • LNA-Molecular Beacons
Peptide nucleic acids (PNA)
  • Genetic diagnostics and therapeutics
  • In situ hybridisation
  • PCR clamping
  • Nucleic acid capture
  • Plasmid vector tagging
  • Duplex DNA targeting
  • Solution-phase hybridisation detection
  • bis-PNAs for selectively targeting any short homopurine sequence in intact double stranded DNA with very high specificity and efficacy
Phosphorothioates (PS-oligos)
  • Thioaptamers for therapeutic and diagnostic applications
  • Phosphorothioate-containing antisense oligos have been used in vitro and in vivo as inhibitors of gene expression