Synthesis Of 3',5'-Dithio-2'-Deoxynucleosides And Study On Their Polymerization

Scientists have studied the origin of nucleic acids for over half a century,but they haven't provided a reasonable explain yet, because it is very difficultto polymerize the phosphorylated nucleosides to nucleic acids. On the otherhand, sulfur as an important role in the origin of life has attracted more andmore interest from the researchers. Although the main compounds in ourpresent organism don't contain sulfur, perhaps sulfur plays a key role in theprocess of the origin of life.As well as known, the mercapto compounds can be easily oxided todisulfides and the disulfides are very stable. In addition, there is sufficientsulfur on the primordial earth. Thus, we proposed a novel hypothesis about theorigin of nucleic acids that the primitive nucleic acids are connected with thedisulfide linkages.In addition, the dithionucleosides can easily react with other compoundsto synthesize a series of disulfur-backboned nucleic acids. Maybe these kindsof nucleic acids can be widely applied to studying nucleic acids probe, biochipand developing the antisense drugs.Based on the above reasons, 3′,5′-dithio-2′-deoxynucleosides were firstlysynthesized starting from 2′-deoxynucleosides. And this provides efficientprocedures to prepare the 3′,5′-dithio-2′-deoxynucleosides. Then theanalytical methods such as HPLC and MS were performed to study on thepolymerization of this kind of nucleosides. Recently we found that this kind ofnucleosides could be easily polymerized to a kind of novel nucleic acids withinternucleotide disulfide linkages and this discovery can offer a strongevidence for our novel hypothesis about the origin of nucleic acids. In addition,we also found that the reactions of 3′,5′-dithio-2′-deoxynucleosides andHCHO could easily afford a novel nucleic acid with internucleotide–S-CH₂-S- linkages under mild conditions and this discovery can provide us agood example to study on the disulfur-backboned nucleic acids. This work isstill on progress. Meanwhile, we discovered that sodium ethanethiol cangreatly improve the sensitivity of 3′,5′-dithio-2′-deoxynucleosides in ESI-MSand this finding makes it become possible to use ESI-MS to study on thepolymerization of 3′,5′-dithio-2′-deoxynucleosides.