Adenosine mixed anhydride formation

The reaction probably proceeds through the formation of an imino analogue of mixed anhydrides by nucleophilic displacement of cyanide during the phosphate activation. Cyanogen bromide was found to be more effective than DISN in this transformation. Since higher yields were obtained in the preparation of the cyclic phosphate from 3 -adenosinc phosphate than from 2/-adenosine phosphate, the authors suggested the formation of an activated... 

A.7.1 Esterification of Acids using Carbodiimides. The formation of anhydrides from carboxylic acids, thiocarboxylic acids, sulfonic acids and phosphorous acids are discussed in Section 2.4.S.2. In this section only special cases of anhydride formation are described. Mixed anhydrides of amino acids and adenylic acid are produced from the corresponding acids using DCC as the condensation agent. ° Mixed anhydrides not containing amino acids, such as butyryl adenate, adenosine 5 -phosphosulfate and p-nitrophenyl-thymidine-5-phosphate are also obtained. 

Figure 11.14 Amino acylation mechanisms catalyzed by aminoacyl-tRNA synthetases The two classes of aminoacyl-tRNA synthetases (aRS s) differ in the site of aminoacylation. Class I aRS s aminoacylate 2 -OH whereas class 11 aRS s add amino acids to 3 -OH of the terminal ribose of the 3 -terminal CCA of cognate tRNA. Magnesinm ions complexed with ATP to enter the active site of aRS may play a dual role in the activation step by both stabilizing the conformation of the ATP (Mg ion bridges the P- and y-phosphates) and participating in adenylate formation (second Mg is found between a- and P-phosphates in some aRS s). In class I aRS, both Lys of MSK and His of HIGH stabilize the bipyramidal oxyphosphorane transition state while R of motif 2 in class II aRS participates in the stabilization of the putative pentacoordinate transition state. The resulting mixed anhydride aminoacyl adenylate is held by the enzyme for the next reaction, i.e. the attack by the 2 -OH (class I) or 3 -OH (class II) of the terminal adenosine at the carbonyl of the aminoacyl adenylate. The amino acid then becomes esterified to the cognate tRNA.

Wittmann s procedure is not suitable for synthesis of P -fluoro-P -5 -adenosine 3 and guanosine triphosphates and diphosphates (9). Syntheses of this type of compound involve formation of the mixed anhydride 2 and its condensation with the corresponding diphosphates (Scheme 4) (9,10a-c). 

Scheme 11.2. The phosphorylation of the carboxylate group of 3-phosphoglycerate to produce a mixed carboxylate-phosphate anhydride, 1,3-bisphosphoglycerate. The phosphoglycerate kinase-catalyzed (EC 2.7.2.3) formation of the anhydride involves the removal of a phosphate group from adenosine triphosphate (ATP), yielding adenosine diphosphate (ADP) and the bisphosphoglycerate. The stereochemistry of the attack at phosphorus is backside to the leaving group.

---