Chemical synthesis phosphodiester

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

Oligoribonucleotides having 2 -5 and 3 -5 -phosphodiester linkages, chemical synthesis of 88YGK753. 

Description of the synthesis of phosphodiesters (prochiral phosphorus center) is beyond the scope of this chapter. Only the chemical synthesis of chiral phos-phomonoesters (4-6) and chiral inorganic phosphates (7) are discussed. The chiral phosphates or chiral phosphorothioates obtained from enzyme reactions are not described in this section. 

The chemical synthesis of oligoribonucleotides containing vicinal 2, 5 - and 3, 5 -phosphodiester links, which are found at the branching site of lariat mRNA during mRNA splicing, has been reviewed.267 The synthesis of a substantial number of triribonucleoside diphosphates (184) has been reported analogues of (184 ... 

In the area of 5 -phosphates, a chemical synthesis of SAICAR (3) has been described, along with a route to carbocyclic AMP and carbocyclic adenylosuccinate. Ferrocene has been attached, via a 5 -phosphodiester and a spacer arm, to thymidine. Subsequent attachment of a thioethanol unit, via a 3 -phosphodiester,... 

Three types of method are used for the chemical synthesis of oligodeoxyribo-nucleotides. The phosphodiester method, in which a nucleotide with a protected 5 -hydroxy group is condensed with a nucleoside-5 -monophosphate with a protected 3 -OH, has been extended by use of the polymer-support method analogous to that used for peptide synthesis. The phosphotriester method has been modified by Narang et al., to use a two-step coupling procedure starting with a nucleotide with a fully masked 3 -phosphate. The most recent type of... 

Damha, M. J, Pon, R. T, and Ogilvie.K. K (1985) Chemical synthesis of branched RNA novel trinucleoside diphosphates containing vicinal 2 -5 and 3 -5 phosphodiester linkages. Tetrahedron Lett 26,4839-4842... 

FIGURE 10 Structure of peptide nucleic acid (PNA). An artificial oligomer produced by chemical synthesis retains the ability to pair with bases, but is resistant to degradation by nucleases because its backbone does not contain the normal phosphodiester linkage. 

Enzymes are protein catalysts that increase the velocity of a chemical reaction, and are not consumed during the reaction they catalyze. [Note Some types of RNA can act like enzymes, usually catalyzing the cleavage and synthesis of phosphodiester bonds. RNAs with catalytic activity are called ribozymes (see p. 436), and are much less commonly encountered than protein catalysts.]... 

Draw the chemical reaction mechanism for the formation of a phosphodiester linkage during DNA synthesis. Discuss the significance of the pyrophosphate product that is formed. What is the significance of the Mg2+ requirement ... 

Phospholipase D (EC 3.1.4.4) is a lipolytic enzyme that hydrolyzes the terminal phosphodiester bond on PLs. Due to its ability to transfer the phosphatidyl moiety of glycerophospholipids to various alcohols (transphosphatidylation), PLD is also used to synthesize PLs with desired head groups that are poorly accessible via the chemical route (Figure 23.4). This ability has been utilized for the synthesis of natural PLs that are rare in nature, such as PG and PS. Novel types of PLs (phosphatidyl-X) have also been synthesized via PLD-mediated transphosphatidylation to add the amphiphilic properties of PLs to the acceptor compounds. These reactions are typically carried out in biphasic systems with water (containing PLD or a hydrophilic alcohol acceptor) and an organic solvent such as chloroform, ether, ethyl acetate, benzene, or toluene. 

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