Phosphate, in DNA

The uracils represent an important class of physiologically active pyrimidines. The bases uracil (XXVIll) and thymine (XXIX) are ubiquitous in nature as constituents of the nucleic acids, where they are linked at the N] position to chains of ribose-5-phosphate (in RNA) and deoxyribose-5-phosphate (in DNA), respectively. 

Even when some scientists thought arsenic could substitute for phosphate in DNA at Mono Lake, other scientists knew that that was not a chemical possibility. The chemists knew that, despite its similarities with phosphate, arsenic cannot form long-lasting bonds in water. Chemistry predicted that phosphate (but not arsenic) could shape the biology of the Mono Lake microbes, which narrowed the possibilities for how those microbes could build DNA. Chemistry narrows down both what can happen and what will happen. 

The importance of phosphate in DNA and RNA macromolecules has been described. It serves as an integral part of the molecular backbone as well as the means by which the monomeric units are connected. It has important binding properties, being able to participate in strong (electrostatic) bonding interactions with metal and amine cations. 

Figure 7.4 The edges of the base pairs in DNA that ate in the major groove are wider than those in the minor groove, due to the asymmetric-attachment of the base pairs to the sugar-phosphate backbone (a). These edges contain different hydrogen bond donors and acceptors for potentially specific interactions with proteins (b).

DNA is not susceptible to alkaline hydrolysis. On the other hand, RNA is alkali labile and is readily hydrolyzed by dilute sodium hydroxide. Cleavage is random in RNA, and the ultimate products are a mixture of nucleoside 2 - and 3 -monophosphates. These products provide a clue to the reaction mechanism (Figure 11.29). Abstraction of the 2 -OH hydrogen by hydroxyl anion leaves a 2 -0 that carries out a nucleophilic attack on the phosphorus atom of the phosphate moiety, resulting in cleavage of the 5 -phosphodiester bond and formation of a cyclic 2, 3 -phosphate. This cyclic 2, 3 -phosphodiester is unstable and decomposes randomly to either a 2 - or 3 -phosphate ester. DNA has no 2 -OH therefore DNA is alkali stable. 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

The phosphate group is derived from phosphoric acid (H3 PO4) by replacing an O—H bond by an O—C or O— P bond. Phosphate is an important functional group in biochemistry, being involved in cellular energy production as well as acting as an important monomer in biopolymers, particularly in DNA. Bonds to phosphate groups form or break in the course of a number of important biochemical reactions. 

Alkylation at several sites on the DNA bases affords an attachment that is chemically stable. Nucleophilic sites that typically yield stable alkyl attachments include the exocyclic nitrogen atoms ISPG, N A, N C, the amide-type nitrogens NIG, NIT, 0 G, and Alkyl groups on phosphate residues in DNA are typically stable... 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Extended solid state n systems facilitate CT, particularly when doped [4-6]. The analogy between DNA and conductive solid state -stacks therefore establishes that a requisite condition for CT may exist in DNA. DNA contains an array of heterocyclic aromatic base pairs, stacked at a distance of 3.4 A, wrapped within a negatively charged sugar phosphate backbone [7] (Fig. 1). The interactions between the n electrons of the DNA base pairs provide the electronic coupling necessary for CT to occur. 

The reaction of X with S must be fast and reversible, close to if not at equilibrium with concentration of S. It can be that there is an intermediate step in which X binds to a protein kinase (a protein which phosphorylates other proteins mostly at histidine residues in bacteria) using phosphate transferred from ATP. It then gives XP which is the transcription factor, where concentration of S still decides the extent of phosphorylation. No change occurs in DNA itself. Here equilibrium is avoided as dephosphorylation involves a phosphatase, though changes must be relatively quick since, for example, cell cycling and division depend on these steps, which must be completed in minutes. We have noted that such mechanical trigger-proteins as transcription factors are usually based on a-helical backbones common to all manner of such adaptive conformational responses (Section 4.11). 

Nucleotide A subunit of DNA or RNA consisting of a purine (adenine and guanine) or a pyrimidine base [thymine (DNA only), uracil (RNA only) and cytosine], a phosphate molecule, and a sugar molecule (deoxyribose in DNA and ribose in RNA). 

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