Modification of oligonucleotides
This service is dedicated to the custom synthesis of oligonucleotide conjugates including oligonucleotides carrying lipids, amino acids, peptides or carbohydrates. In addition, they may include other modifications such as phosphorothioate linkages, 2’-O-methyl-RNA, 2’-O-MOE-RNA, 2′-F-RNA, Locked nucleic acids (LNA), modified nucleotides. The oligonucleotides will be prepared in 1 micromol scale. In most cases, the preparation of the conjugates will require the preparation of oligonucleotides carrying reactive groups such as; amino or thiol groups, which will be subjected to a post-synthetic modification. Purification and characterization will include reversed-phase HPLC analysis and mass spectrometry (MALDI-TOF).
Modification of oligonucleotides during and post synthesis to meet user requirements:
- Conjugation of oligonucleotides with fluorophores (fluoresceine, Cy3, Ct5, etc..) and other types of small molecules such as biotine, lipids.
- Conjugation to peptides.
- Phosphorothioate linkages
- Modified backbones such as locked nucleic acids (LNA), 2’-O-alkyl-RNA, etc..
- Modified nucleobases: 2-aminopurine, 5-methyl-dC, etc…
- 5’, 3’-modifications such as 5’-, 3’-amino, 5’-, 3’-thiol, etc..
Customer benefits
The service benefits from the 40-years’ experience of the researchers participating in the service, with hundreds of scientific communications on improving the methodology used for the synthesis of modified oligonucleotides. This includes fatty acid derivatives, amino acids, cell penetrating peptides and carbohydrates not available from other services. In addition, the service can develop customized solutions for molecules not addressed in the bibliography.
Target customer
The primary audience are research groups and companies working on gene therapy and gene inhibition in the early stages of preclinical development.
References
1) “Aptamer-peptide conjugates as a new strategy to modulate human α-thrombin binding affinity”. Aviñó, A. et al. Biochim. Biophys. Acta (General subjects), 1863, 1610-1630 (2019).
2) “Synthesis of oligonucleotides carrying amino-lipid groups at the 3’-end for RNA interference studies”. Grijalvo, S. et al. J. Org. Chem., 75, 6806-6813 (2010).
3) “Synthesis and evaluation of 3’ oleyl-oligonucleotide conjugates as potential cellular uptake enhancers”. Navarro, N. et al. SYNLETT, in press (2024). doi: 10.1055/s-0042-1751528.