Chiral oligonucleotide synthesis addresses the stereochemical complexity introduced by phosphorothioate (PS) linkages, where each phosphorothioate linkage introduces a chiral phosphorus center (Rp or Sp configuration).
In conventional phosphorothioate oligo synthesis, these linkages are typically formed as mixed stereochemical populations, resulting in heterogeneous products.
Stereospecific oligo synthesis enables controlled formation of phosphorothioate linkages with defined stereochemistry, supporting programs that require greater molecular uniformity, structured backbone design, or sequence-specific stereochemical exploration.
Depending on program goals, this may include fully stereopure oligonucleotides, partially defined stereochemical patterns, or targeted stereochemical optimization at selected backbone positions.
These approaches are relevant to antisense, siRNA, and other advanced oligonucleotide platforms where backbone design can influence overall behavior.
stereodefined phosphorothioates
reduced heterogeneity
sequence-level control
development-stage optimization
advanced oligo design
Figure: Representative comparison of stereopure versus conventional stereorandom phosphorothioate oligonucleotides.
chiral backbone design platform
Define • Pattern • Optimize
Flexible stereochemical design strategies for phosphorothioate oligonucleotides, from conventional mixed backbones to targeted stereodefined and fully stereopure constructs.
Stereopure
Full control
Defined backbone stereochemistry across the sequence
Patterned
Selective definition
Targeted Rp/Sp assignments at chosen positions
Conventional
Mixed PS
Standard stereorandom phosphorothioate backbone population