Nucleotide 2 -deoxyadenosine monophosphate

Diepoxybutane also reacts with nucleosides, nucleotides and DNA. Adducts at N of adenine were identified in incubations (pH 7) containing deoxyadenosine, deoxyadenosine monophosphate or poly(dA-dT)(dA-dT), as determined by mass spectrometry, or calf tliymus DNA as determined by a high-performance liquid chromatography/ 32P-postlabelling method (Leuratti et al., 1994). By the latter method, the authors demonstrated adduct formation to N of adenine in DNA from Chinese hamster ovary cells incubated with diepoxybutane at 37°C. 

Dietary purines are largely catabolized in the gut, rather than used by the body for the synthesis of nucleic acids. The end-product of purine catabolism in humans is uric add. The diet accounts f[ir less than half of the uric add appearing in the bloodstream, Most of the plasma uric add, or urate, originates from catabolism of the purines synthesized by the body (endogenous purines). The major purines are adenine and guanine. They occur mainly as nucleotides, such as adenosine triphosphate (ATP) and guanosine triphosphate (GTP), and as parts of nucleic acids. For example, the adenine in (UvfA occurs as adenosine monophosphate, and the adenine in DNA occurs as deoxyadenosine monophosphate. 

Adefovir is a nucleotide analog of deoxyadenosine monophosphate that is active against retroviruses (like HIV), herpes viruses, and hepadnaviruses. Adefovir dipivoxil 10 mg by mouth once daily for 48 weeks has been approved for use in adult patients with chronic HBV who are either treatment naive or have lamivudine-resistant... 

In order to determine the stereochemical course of the nonenzymic hydrolysis of cyclic nucleotides, and in particular to examine the role of pseudorotation, Gerlt and coworkers carried out a chiral phosphate analysis of the base-catalysed hydrolysis of cyclic deoxyadenosine monophosphate (Mehdi et al., 1983). In 0.2 m Ba(OH)2 at lOO C, cdAMP hydrolyses to a mixture of 3 dAMP and 5 dAMP. The position of label incorporation on hydrolysis in labelled water indicates P—O as opposed to C—O bond cleavage. The overall stereochemistry of hydrolysis was followed by recycliz-ing and analysing both the ring-opened products of ( O, 0) cdAMP hydrolysis (Scheme 31). 

Write a structural formula for the nucleotide deoxyadenosine-5 -monophosphate. 

Figure 2 UV spectra of the DNA nucleotides deoxyadenosine 5 -monophosphate (A), deoxyguanosine 5 -monophosphate (G), deoxycytidine 5 -monophosphate (C) and thymidine 5 -mono-phosphate (T). The spectrum of uracil Is almost Indistinguishable from that of thymine.

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

In nature, eight common nucleotides exist, four found in DNA and four in RNA. In the standard abbreviations for DNA nucleotides, a lowercase d specifies the presence of deoxyribose. RNA nucleotides lack this designation. Nucleosides have names of one word (e.g., deoxyadenosine, cytidine, and uridine). The ending monophosphate completes the nucleotide names. Table 16.1 lists correct names for all common nucleotides and nucleosides, and Figure 16.9 shows linkages and structures for all eight nucleotides. 

Nucleotides are nucleosides that have been phosphorylated on the 5 -hydroxyl group. One, two, or three phosphates can be added. Nucleotides are generally named by appending monophosphate, diphosphate, or triphosphate to the end of the name of the corresponding nucleoside, and the names are typically abbreviated. The suffixes -MP, -DP, and -TP correspond to mono-, di-, and triphosphate, respectively. Examples of 2 -deoxyadenosine 5 -diphosphate or ADP (6.13) and uridine 5 -monophosphate or UMP (6.14) are shown in Figure 6.5. 

We have previously reported the syntheses and configurational analyses of the diastereomers of cyclic 2 -deoxyadenosine 3, 5 -[170, 180]monophosphate (13) and the stereochemical course of the hydrolysis of one of the diastereomers catalyzed by the cyclic nucleotide phosphodiesterase from bovine heart (12). In this communication we report the syntheses and configurational assign-1 Current address Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143... 

Nucleotides differ from nucleosides in that they have phosphate groups attached to either the 3 or 5 position of the sugar. The structures of deoxyadenosine 5 -monophosphate,... 

A-residue, G-residue etc. or more simply dA, dG (or A, G etc. where there is no possibility of confusion with the ribonucleotides, for example as in a DNA sequence) pdT etc. dTMP, dAMP etc. rATP, rCTP etc. A deoxyadenosine (deoxyguanosine) monophosphate either at one end, or within, a polynucleotide chain and linked to the adjacent nucleotide(s) by phosphodiester bond(s) deoxythymidine 5 -monophosphate the deoxynucleoside 3 -monophosphate the ribonudeoside triphosphates, adenosine triphosphate, cytidine triphosphate etc. 

Carbohydrates, commonly referred to as sugars and starches, are polyhydroxy aldehydes and ketones, or compounds that can be hydrolyzed to them. The cellulose in plant stems and tree trunks and the chitin in the exoskeletons of arthropods and mollusks are all complex carbohydrates. Four examples are shown in Figure 27.1. They include not only glucose and cellulose, but also doxorubicin (an anticancer drug) and 2 -deoxyadenosine 5 -monophosphate (a nucleotide base from DNA), both of which have a carbohydrate moiety as part of a larger molecule. 

Adefovir is an antiviral agent that inhibits hepatitis B virus (HBV) DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. Adefovir is indicated in the treatment of chronic hepatitis B in adults with evidence of active viral replication and evidence of persistent elevations in serum aminotransferases or histologically active disease. Adefovir dipivoxil (9-[2-[bis[(pivaloyloxy)methoxy] phosphinyl]methoxyl]ethyl]adenine, bis-POM PMEA) is a diester prodrug of adefovir, an acyclic phosphonate nucleotide analog of adenosine monophosphate. 

The synthesis of the two diastereoisomers of P -l-(2-nitrophenyl)ethyl adenosine S -lri-phosphate (91) has been achieved using resolved (R)- and (5)-l-(2-nilroidienyl)ethanol. The alcohols were converted to (R)- and (5)-l-(2-nitrophenyl)ethyl phosphates by phosphitylation with N,)V-diisopropyl-fi(s-(2-cyanoethyl)phosphoramidite (92) and subsequent oxidation with 3-chlorobenzoic acid. Each of the monophosphates was activated with carbonyidiimidazole and condensed with adenosine diphosphate to give the desired triphosphate. These ATP analogues can be used for the rapid release (by flash photolysis) of ATP in biological systems. The 8-azido-3 -0-anthraniloyl derivatives of 2 -dADP (93) and 2 -dATP (94) have been prepared in seven steps from 8-azido-2 -deoxyadenosine. These compounds are of interest as fluorescent and photoactivatable probes for the nucleotide binding site of kinases and cyclases. In particular, (94) was shown to be a competitive inhibitor of Bordetella pertussis adenylate cyclase and the observed K- (74 pM) was close to tiiat predicted from the K- value of 3 -0-anthraniloyl-2 -dATP. ... 

The nucleotides are 2-deoxyadenosine 5 -monophosphate (dAMP), 2-deoxythymidine 5 -monophosphate (dTMP), 2-deoxyguanosine 5 -monophosphate (dGMP), and 2-deoxy-cytidine 5 -monophosphate (dCMP). 

The kinase which converts deoxycytidine to its 5 -monophosphate has been studied most extensively in preparations from calf thymus 35, 36). The preferred substrate is deoxycytidine, for which the Michaelis constant (5 X 10 M) is much lower than that of two other substrates, deoxyadenosine and deoxyguanosine. Cytidine, uridine, and thymidine are not phosphorylated by this enzyme. Deoxycytidine kinase is subject to a complex pattern of allosteric regulation by nucleotides. The end product of deoxycytidine phosphorylation, dCTP, is a potent inhibitor this inhibition is reversed by dTTP. The enzyme has a rather broad specificity for the phosphate donor, with the triphosphates of the natural ribo- and deoxyribonucleosides being substrates the inactivity of dCTP is a notable exception. 

Among the frequently studied DNA components are nucleotides and nucleosides. A number of the DNA-like conformations of the isolated nucleotides have been revealed. The S/anti conformation is the most favorable for 2 -deo thymi-dine monophosphate (mTMP), 2 -deoxycytidine (mCMP), and 2 -deoxyadenosine (mAMP) S/syn conformation is favorable for 2 -monophosphate deoxyguanosine (mGMP). Coirformers with the syn orientation of nucleobase, relative to the sugar moiety, exist only in the case of mGMP. However, conformers with an orthogonal orientation of the nucleobase relative to the sugar moiety are found in mCMP mAMP molecules. 

The base plus the sugar group (without the phosphate group) is called a nucleoside. Nucleosides are named from the bases. For example, the nucleoside composed of adenine with jS-D-ribose is called adenosine. The nucleoside composed of adenine with 2-deoxy-j8-D-ribose is called deoxyadenosine. A nucleotide is named by adding monophosphate (or diphosphate or triphosphate) after the nucleoside name. A number with a prime indicates the position of the phosphate group on the ribose ring. Thus, adenosine-5 -monophosphate is a nucleotide composed of adenine, jS-D-ribose, and a phosphate group at the 5 position of jS-D-ribose. 

These compounds illustrate the structural diversity of carbohydrates. Glucose is the most common simple sugar, whereas cellulose, which comprises wood, plant stems, and grass, is the most common carbohydrate in the plant world. Doxorubicin, an anticancer drug that has a carbohydrate ring as part of its structure, has been used in the treatment of leukemia, Hodgkin s disease, and cancers of the breast, bladder, and ovaries. 2 -Deoxyadenosine 5 -monophosphate is one of the four nucleotides that form DMA. 

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