title: In vitro and in vivo biophysical properties of oligonucleotides containing 5'-thio nucleosides.
abstract: Phosphorothioate modification is one of the most widely investigated and promising chemical modifications in oligonucleotide (ON) based therapeutics. Structurally similar 5'-thio or phosphorothiolate-modified nucleotides, in which a 5'-bridging oxygen is replaced with a sulfur atom, are gaining importance for ON-based research. Several reports have been published describing the synthesis of 5'-thio-modified ONs but no detailed in vitro and in vivo data are available. Here, we report the synthesis of 5'-thio-modified 2'-deoxy-5-methylcytidine. 5'-Thio-modified thymidine and 2'-deoxy-5-methylcytidine were incorporated into target ONs, then we evaluated their binding affinity, nuclease stability, RNase H mediated scission, stability in blood serum, and in vitro and in vivo activity. This is the first report showing the influence of 5'-thio-modified antisense ONs in in vitro and in vivo experiments.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University.
authors.forename: Md Ariful
authors.initials: MA
authors.lastname: Islam
authors.forename: Reiko
authors.initials: R
authors.lastname: Waki
authors.forename: Aki
authors.initials: A
authors.lastname: Fujisaka
authors.forename: Kosuke Ramon
authors.initials: KR
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Obika
mesh_terms: D000818:Animals; D004355:Drug Stability; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000737:chemistry*; D016914:Ribonuclease H / Q000378:metabolism; D013872:Thionucleosides / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D013872:Thionucleosides; D016914:Ribonuclease H