The stability of oligonucleotide duplexes and protein-oligonucleotide complexes is determined by the conformation and dynamics of the sugar fraction. The conformation of ribofuranose sugars plays an important role in the structure and dynamics of functional nucleic acids such as siRNAs, aon, aptamer, and miRNAs. To improve stability, some chemical modifications are introduced into the sugar group. Sugar ring modifications can impact the local conformational dynamics and also the global helical properties of dsRNA; this in turn can contribute to the recognition, binding, and cleavage activity of the proteins involved in RNAi. The most common and effective strategy is to modify the 2'-position of furanose. These modifications make the sugar shrinking favor the 3'-endo conformation, improving the thermal stability of oligonucleotides, increasing the affinity of oligonucleotides for complementary RNAs, and reducing off-target effects and unwanted immunogenic responses.
Fig.1 Structure of the 2'-O-modifications. (Egli, et al., 2005)
The sugar ring in the nucleotide unit is flexible and continuous interconversions among the countless puckered forms are possible. At CD BioGlyco, we use different substituents at the furanose ring, that tune the sugar puckering in a certain direction by imposing various stereo-electronic and steric effects.
The modification services we provide include the 2' modifications, 2'-4'-dual modifications, and 2'-5'-dual modifications. Specifically, we provide accurate modifications to introduce functional groups at the 2'-position of the sugar ring, such as 2'-methoxy (2'-OMe), 2'-O-methoxyethyl, 2'-amino (2'-NH2), etc. The nucleic acid modified by the sugar ring greatly improves the biological stability of the sequence.
We provide a complete extraction, separation, and purification service. Appropriate protection reagents are selected during synthesis and modification to avoid by-products at other sites. At the same time, we will provide you with the synthetic route, infrared spectrum nuclear magnetic spectrum of the product, etc.
Fig.2 The process of modified synthesis service. (CD BioGlyco)
CD BioGlyco provides high-quality Custom Carbohydrate Synthesis services to clients all over the world. Moreover, we provide efficient Customized Sugar-nucleotide Services including but not limited to Phosphorylation Modification, Phosphorothioate Backbone Modification, Base Modification, Linker Modification, and Fluorophore Modification. If you are interested in our services, please feel free to contact us.
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