Nucleoside-like molecule

Nucleoside monomers with the DNA base replaced by fluorescent hydrocarbons and heterocycles, and their assembly into DNA-like molecules in which the all bases are fluorescent 06OBC4265. 

Here 1 have let X and F stand for any of the four nucleosides of RNA. Note that the first step results in a triphosphate gronp at the 5 end of the RNA nucleotide chain. Each additional nncleoside triphosphate extends the chain by one unit with splitting ont of inorganic pyrophosphate, PPi. So at some point, the growing RNA molecule will look like ... 

The constrained nucleosides are of interest as leads for small-molecule therapeutics. For example, the (3-2 -0,3 -C-oxetane analogues of the antiviral 3 -azido-3 -deoxythymidine (AZT), which exist predominantly in the E-like conformation (see, for example, Equation 55), were investigated for inhibition of human immunodeficiency virus 1 (HIV-1). Neither the modified nucleosides nor their 5 -monophosphate analogues inhibit HIV-1, supporting a hypothesis that reverse transcriptase inhibitors must have conformational freedom <2001JOC4878, 2002J(P1)1655>. 

An important protecting group developed specifically for polyhydroxy compounds like nucleosides is the tetraisopropyl-disiloxanyl group, abbreviated TIPDS, that can protect two alcohol groups in a molecule. 

Even though the hydrolysis of the nucleoside triphosphates has a large negative AG, the polymerization reaction as written still has a positive AG at concentrations present in a cell and in laboratory reactions (+0.5 kcal/mol = 2.1 kJ/mol). Thus, in the absence of any other reaction DNA polymerases would catalyze depolymerization rather than polymerization. Indeed, if excess pyrophosphate and a polymerase are added to a solution containing a partially replicating DNA molecule, the polymerase acts like a nuclease. In order to drive the reaction to the right, pyrophosphate must be removed, and this is... 

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