Synthesis and properties of 4'-ThioDNA: unexpected RNA-like behavior of 4'-ThioDNA.
The synthesis and properties of fully modified 4'-thioDNAs, oligonucleotides consisting of 2'-deoxy-4'-thionucleosides, were examined. In addition to the known literature properties (preferable hybridization with RNA and resistance to endonuclease hydrolysis), we also observed higher resistance of 4'-thioDNA to 3'-exonuclease cleavage. Furthermore, we found that fully modified 4'-thioDNAs behaved like RNA molecules in their hybridization properties and structural aspect, at least in the case of the 4'-thioDNA duplex. This observation was confirmed by experiments using groove binders, in which a 4'-thioDNA duplex interacts with an RNA major groove binder, lividomycin A, but not with DNA groove binders, to give an increase in its thermal stability. Since a 4'-thioDNA duplex competitively inhibited the hydrolysis of an RNA duplex by RNase V1, it was not only the physical properties but also this biological data suggested that a 4'-thioDNA duplex has an RNA-like structure.
Inoue
Naonori
N
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Minakawa
Noriaki
N
Matsuda
Akira
A
D002942:Circular Dichroism; D003850:Deoxyribonuclease I / Q000378:metabolism; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D043264:Phosphodiesterase I / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D013872:Thionucleosides / Q000138:chemical synthesis / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D013872:Thionucleosides; D012313:RNA; D003850:Deoxyribonuclease I; D043264:Phosphodiesterase I; C470790:phosphodiesterase I, snake venom