Oligonucleotide charge reversal: 2'-O-lysylaminohexyl modified oligonucleotides.
A novel cationic building nucleoside building block designed for antisense and siRNA oligonucleotides is presented. Protected L-lysine was coupled to 2'-O-aminohexyluridine and the resulting nucleoside was phosphitylated for automated oligonucleotide synthesis. An increasing number of these 2'-O-lysylaminohexyl nucleosides lowered the melting temperature of desoxy-thymidine homododecamers, but the decrease was lower than that for DNA/RNA hybrids. Incubation with an exonuclease showed the exceptionally high resistance against enzymatic degradation. CD spectrometry revealed a gradual transition towards an A-type oligonucleotide structure. Based on these data, the cationic building block is particularly suited for gapmer antisense as well as siRNA oligonucleotides.
Department of Medicinal Chemistry, University of Vienna, Vienna, Austria. johannes.winkler@univie.ac.at
Johannes
J
Winkler
Christian R
CR
Noe
D002942:Circular Dichroism; D004355:Drug Stability; D004563:Electrochemistry; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000737:chemistry; D013816:Thermodynamics
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering