Nucleoside 5 -triphosphate chemical synthesis

As already mentioned, a continual inflow of energy is necessary to maintain the stationary state of a living system. It is mostly chemical energy which is injected into the system, for example by activated amino acids in protein biosynthesis (see Sect. 5.3) or by nucleoside triphosphates in nucleic acid synthesis. Energy flow is always accompanied by entropy production (dS/dt), which is composed of two contributions ... 

Several chemical and enzymatic methods are available for the synthesis of glycosyl phosphates. The required nucleoside triphosphates (NTPs) are most conveniently prepared by enzymatic routes. In general, these methods involve the sequential use of two kinases to transform NMPs to NTPs, by the corresponding NDPs (Fig. 2, see a recent review [12] for more details). 

Scheme 37 Second and third stages of the evolution of amino acid activation (2) The system of Scheme 39 is improved by enzyme catalysis the mixed anhydride is stabilized by binding making the equilibrium with NCA more favorable (3) an alternative pathway for nucleoside triphosphate synthesis has been introduced, the chemical flux has been reverted...

Different types of antitemplates can be and, presumably, will be, synthesized by employing other chemical reactions that are sufficiently mild and selective for the modification of polynucleotides. Another approach to this problem is, of course, to synthesize an appropriately modified nucleoside triphosphate and utilize it as one of the substrates in a DNA or RNA polymerizing system, in the presence of the specific template for which an antitemplate is to be made. The enzymatic synthesis method has some obvious advantages however, the inhibitory activity of the product (antitemplate) may limit its applications. 

Cofactor Regeneration - About 70% of enzymes use nucleoside triphosphates, nlcotlnetmlde derivatives [NAD(P)(H)], or CoA as cofactors. These enzymes include many of those of greatest Interest In the synthesis of fine chemicals. Since these cofactors are too expensive to be used stoichiometrically, it has been necessary to develop recycling systems for them. The problem of recycling the nucleoside triphosphates... 

Polymerase enzymes are used extensively in the laboratory for the synthesis and manipulation of DNA and RNA (44). One of the most important applications of enzymatic DNA synthesis is in the polymerase chain reaction (PGR), which is used to amplify minute quantities of DNA from a variety of soin-ces, inclnd-ing crime scene evidence, archaeological specimens, or medical samples (45). In PGR, two short oligonucleotide primers are first synthesized by chemical methods. These primers are complementary to the 5 -ends of the two strands which form the DNA duplex of interest (Fig. 11). A large excess of the primers is mixed with the target DNA along with a DNA polymerase enzyme and the nucleoside triphosphate monomers. The sample is heated to disrupt the target duplex. Then, as the... 

Carhodiimidazole-Catalyzed Chemical Synthesis of Arylazido Adenine Nucleotide Analogs. The utilization of carbodiimidazole to facilitate the formation of activated carboxylic acids was elegantly applied by Gottikh and his group to the synthesis of a wide spectrum of aminoacyl nucleosides, nucleotides, nucleoside di- and triphosphates, and tRNA derivatives. The formation of an imidazolide intermediate has been used in our work in the synthetic schemes leading to the esterification of adenosine and diphosphopyridine nucleotides. 

The same authors proposed another interesting improvement to the synthesis of NTPs, namely an ionic-tag-assisted approach. They noticed that chemical syntheses of nucleoside triphosphates suffer from difficulties in isolation of the desired product from inorganic... 

We have discussed modified nucleoside phosphoramidites (Section 2.1) and modified nucleoside triphosphates (Section 5.1) and their uses as the monomers for chemical or enzymatic synthesis of modified oligomers (oligonucleotides and oligodeojqmucleotides). In this section, our emphasis is primarily on interesting properties of modified oligomers. 

This chapter reviewed selected papers published in 2012 on the chemical synthesis and biological, particularly medicinal, applications of nucleotides and oligonucleotides. The term nucleotide is the central point of the chapter. As a nucleotide has a nucleoside in its make-up and plays its functional roles as part of oligonucleotides, some relevant aspects of nucleosides and oligonucleotides are also included in this chapter. For its intended functions, a nucleotide can be presented in several forms, such as phosphoramidite, phosphoramidate, phosphonate and triphosphate, their relationships can be summarized in the Scheme below. 

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