Satoshi Obika

Xeno nucleic acids (XNAs) are a group of chemically modified nucleic acid analogues that have been applied to various biological technologies such as antisense oligonucleotides, siRNAs and aptamers.

Towards the next generation: New LNA analogues based on a cyclic amide structure, termed amido-bridged nucleic acids (AmNAs), have been synthesized. Oligonucleotides modified with these residues showed high nuclease resistance along with high binding affinities towards complementary strands. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the aut

Recent findings in molecular biology implicate the involvement of proprotein convertase subtilisin/kexin type 9 (PCSK9) in low-density lipoprotein receptor (LDLR) protein regulation. The cholesterol-lowering potential of anti-PCSK9 antisense oligonucleotides (AONs) modified with bridged nucleic acids (BNA-AONs) including 2',4'-BNA (also called as locked nucleic acid (LNA)) and 2',4'-BNA(NC) chemistries were demonstrated both in vitro and in vivo. An in vitro transfection study revealed that all

Restricting the sugar moiety of a nucleic acid to a single conformation can be accomplished by forming a bridge in the sugar.A large number of bridged nucleic acids with variable bridged structures and conformations have been developed.The synthesis and properties of these artificial nucleic acid analogues are discussed.Such conformational restriction of the sugar moiety significantly improved the properties of the nucleic acid.

Significantly enhanced binding affinity to C⋅G base pairs without loss of sequence selectivity is achieved by using a nucleotide containing a 2-pyridone and a 2'-O,4'-C-methylene-bridged nucleic acid analogue (P^B , see picture). The degree of stabilization of the triplex formed enables C⋅G interruptions in a homopurine⋅homopyrimidine double-stranded DNA to be detected.

Novel bicyclic nucleoside analogues 3′-O,4′-C-methyleneribonucleosides 1 are conveniently prepared starting from uridine; the sugar puckering of 1 is found to be nearly in the S-conformation by means of PM3 calculations and 1 H NMR studies.

Hydrogen peroxide (H₂O₂) is a reactive oxygen species (ROS) involved in various diseases, including neurodegeneration, diabetes, and cancer. Here, we introduce a new approach to use H₂O₂ to modulate specific gene expression in mammalian cells. H₂O₂-responsive nucleoside analogues, in which the Watson-Crick faces of the nucleobases are caged by arylboronate moieties, were synthesized. One of these analogues, boronated thymidine (<b

A novel 2',4'-BNA/LNA analog bridged by guanidine, termed as guanidine bridged nucleic acid (GuNA), was synthesized and incorporated into oligonucleotides. Thermal stabilities and nuclease resistance of GuNA-modified oligonucleotides were investigated and compared with those of 2',4'-BNA/LNA and natural DNA oligonucleotides. GuNA exhibited interestingly high binding affinity towards complementary ssDNA than 2',4'-BNA/LNA.

High scalability of a novel bicyclic nucleoside building block, amido-bridged nucleic acid (AmNA), to diversify pharmacokinetic properties of therapeutic antisense oligonucleotides is described. N2'-functionalization of AmNA with a variety of hydrophobic groups is straightforward. Combinations of these modules display similar antisense knockdown effects and improve cellular uptake, relative to sequence-matched conventional 2',4'-bridged nucleic acid (2',4'-BNA) in vivo.