3 -Phosphorylated adenosine derivative

The enzyme catalyzes the deamination of a wide spectrum of naturally occurring adenosine derivatives including, in addition to the majority of compounds noted in Table VII, many other phosphorylated derivatives (75, 179). The Km values for adenosine, 5 -AMP, 3 -AMP, 3, 5 -cyclic AMP, and 2 -dAMP ranged from 0.1 to 0.5 mM. Except for 2 -dAMP, the relative rates of deamination for these compounds were similar. The 2 -monophosphate ester was not deaminated (75, 180). Oligomers of AMP such as ApA, ApAp, ApApA, and ApApApA (181) were also substrates deamination of the first residue of ApAp was more rapid than the second. Deamination of polyadenylic, polydeoxyadenylic, and the terminal residue of E. coli soluble RNA was not observed. 

FIGURE 18.8 Coenzyme A is derived from a phosphorylated adenosine diphosphate (ADP) and pantothenic acid bonded by an amide bond to aminoethanethiol, which contains the — SH reactive part of the molecule. 

The interesting observation has been made that 3 -amino-3 -deoxy-adenosine as a suspension in phosphoryl chloride-triethyl phosphate at 4° is converted into the 5 -chloro-5 -deoxy derivative in 80% yield, but that predissolution of the nucleoside in triethyl phosphate, followed by treatment with phosphoryl chloride at 0°, yields the 5 -phosphate in 62% yield.382... 

For many years, niclosamide (Niclocide) was widely used to treat infestations of cestodes. Niclosamide is a chlorinated salicylamide that inhibits the production of energy derived from anaerobic metabolism. It may also have adenosine triphosphatase (ATPase) stimulating properties. Inhibition of anaerobic incorporation of inorganic phosphate into ATP is detrimental to the parasite. Niclosamide can uncouple oxidative phosphorylation in mammalian mitochondria, but this action requires dosages that are higher than those commonly used in treating worm infections. 

Another important biochemical compound derived from adenine is adenosine triphosphate (ATP). ATP plays a critical role in supplying energy in organisms to support metabolism. ATP is a nucleotide similar to RNA. In ATP the base is adenine and the phosphorus group is a three-phosphoryl (P032 ) chain. 

Reduction of l,10-phenanthroline-2-aldehyde to 1,10-phenanthroline-2-carbinol is efficiently accomplished by a dihydronicotinamide derivative in acetonitrile solution catalyzed by zinc ions. This was the first example of the reduction of an aldehyde by a NADH analog in a nonenzymic system. It also supports the catalytic function of the metal ion in the enzymic system.359 l,10-Phenanthroline-2-carbinol, obtained by sodium borohydride reduction of 2-carbomethoxy-1,10-phenanthroline, is phosphorylated by adenosine triphosphate in the presence of zinc ions.360... 

Organisms of all biological kingdoms convert 64 into the cys-teamine derivative phosphopantetheine (65) using L-cysteine as substrate. 65 is converted to coenzyme A (66) by attachment of an adenosine moiety via a pyrophosphate linker and phosphorylation of the ribose moiety. Phosphopantetheine can be attached covalently to serine residues of acyl carrier proteins that are parts of fatty acid synthases and polyketide synthases. 

The synthesis and incorporation into oligonucleotides of the A-phosphory-lated deoxycytidine 3 -phosphoramidites (144) and (145) obtained either from the O-protected 2 -deoxycytidine and bis(2-cyanoethyl) A,A-diisopropyl phosphoramidite or diethylphosphorochloridite, respectively, was described by Sekine. Sekine also reported that the A-phosphorylated derivatives of 2 -deoxy adenosine decomposed readily and were unsuitable for incorporation into oligodeoxynucleotides. 

Adenosine and adenosine triphosphate (ATP), its phosphorylated derivative, have been used to treat acute paroxysmal supraventricular tachycardias and adenosine has also been used in the diagnosis of narrow-and broad-complex tachycardias (SEDA-16,176). 

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