The synthesis of di- and oligo-nucleotides containing a phosphorodithioate internucleotide linkage with one of the sulfur atoms in a 5'-bridging position.
A new type of internucleotide phosphorodithioate linkage is described, wherein one of the sulfur atoms occupies a 5'-bridging position. Representative dinucleotides possessing such a bond were synthesized by S-alkylation of nucleoside-3'-O-phosphorodithioates with 5'-halogeno-5'-deoxy-nucleosides. A fully protected dithymidylate containing internucleotide 5'-S-phosphorodithioate linkage was converted into a 3'-O-phosphoramidite derivative and employed for introduction of a modified dinucleotide into a predetermined position of the oligonucleotide sequence. The 5'-S-phosphorodithioate linkage in dinucleotide analogues was found to be resistant toward nucleolytic degradation with snake venom PDE and nuclease P1. However, P-stereoselective degradation was observed for diastereomers of 5'-S-phosphorodithioate dithymidine analogs under treatment with calf spleen PDE. The new 5'-S-phosphorodithioate linkage was readily degraded by iodine solutions in the presence of water. It was also found that oligothymidylates containing a single 5'-S-phosphorodithioate linkage form much weaker duplexes with their complementary sequences.
Olesiak
Magdalena
M
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Stec
Wojciech J
WJ
Okruszek
Andrzej
A
D015226:Dinucleoside Phosphates / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D009841:Oligonucleotides / Q000737:chemistry; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis*; D010710:Phosphates / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*
D015226:Dinucleoside Phosphates; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D009946:Organothiophosphorus Compounds; D010710:Phosphates; D013455:Sulfur; C083120:phosphorodithioic acid