2 -Deoxyadenosine 5 -diphosphate dADP

Adenine Deoxyadenosine Deoxyadenyiic acid Deoxyadenosine monophosphate (dAMP) Deoxyadenosine diphosphate (dADP) Deoxyadenosine triphosphate (dATP)... 

When two acid molecules condense by elimination of a molecule of water, the product is called an acid anhydride, as can be seen in Figure 12.60. Acid anhydrides are always very reactive, or high-energy, compounds. When deoxy-adenosine monophosphate forms an anhydride with phosphoric acid, we have deoxyadenosine diphosphate (dADP). Of course, if we add an additional phosphate group, we have deoxyadenosine triphosphate (dATP). 

The overall reaction for the synthesis of, for example, deoxyadenosine diphosphate (dADP)... 

Scheme 14.11. A proposal for the use of ribonucleoside diphosphate reductase (ribonucleotide diphosphate reductase, EC 1.17.4.1) to convert adenosine diphosphate (ADP), uridine diphosphate (UDP), and cytidine diphosphate (CDP) into their respective 2 -deoxy analogues deoxyadenosine diphosphate (dADP),deoxyuridine diphosphate (dUDP),and deoxy-cytidine diphosphate (dCDP), or, in general, ribonucleic acids (RNAs) into the corresponding deoxyribonucleic acids (DNAs) (after Stubbe, J. 7. Biol. Chem., 1990,265, 5330).

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 E. coli DNA polymerase I (Pharmacia 3427-0626 E. coli CM 5197), an enzyme already known to be multifunctional (the polymerase and the 3, 5 -exonuclease activity belong to the same polypeptide chain and can be split off only proteolytical-ly) has still other, as yet imsuspected, capabilities. It deaminates 2 -deoxyadenosine to make 2 -deoxyinosine, and reduces ADP to dADP in the presence of dGTP and NADPH. The multifunctional enzyme from E. coli is also active as a nucleoside diphosphate kinase. This last activity has also been observed by A. Kornberg (6). 

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