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.
Winkler
Johannes
J
Department of Medicinal Chemistry, University of Vienna, Vienna, Austria. johannes.winkler@univie.ac.at
Noe
Christian R
CR
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