Synthesis and biophysical properties of constrained D-altritol nucleic acids (cANA).
The first synthesis of constrained altritol nucleic acids (cANA) containing antisense oligonucleotides (ASOs) was carried out to ascertain how conformationally restricting the D-altritol backbone-containing ASO (Me-ANA) would affect their ability to form duplexes with RNA. It was found that the thermal stability was reduced (cANA/RNA -1.1 °C/modification) compared to DNA/RNA, suggesting the constrained system results in a small destabilizing perturbation in the duplex structure.
Department of Medicinal Chemistry, Isis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, California 92010, USA. mmigawa@isisph.com
Michael T
MT
Migawa
Thazha P
TP
Prakash
Guillermo
G
Vasquez
Punit P
PP
Seth
Eric E
EE
Swayze
D004247:DNA / Q000737:chemistry; D015394:Molecular Structure; D009696:Nucleic Acids / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D013237:Stereoisomerism; D013402:Sugar Alcohols / Q000737:chemistry*
D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D013402:Sugar Alcohols; C042890:altritol; D012313:RNA; D004247:DNA