Cordycepin-5 -triphosphate

Cordyceps militaris (fungus) Metabolite Cordycepin-5 -triphosphate yields 3 -Deoxyadenosine-5-monophosphate (3 -dAMP)... 

Dissolve 100 pCi lyophilised [a-32P] cordycepin-5 -triphosphate with the denatured RNA solution. 

Azacytidine 2, 3, 5 -Tri-Ac, A-887 6-Azacytidine 2, 3, 5 -Tribenzoyl, A-887 6-Azacytidine, A-887 8-Azaguanosine 5 -Phosphate, A-888 6-Azathymidine 3, 5 -Diphosphate, A-891 6-Azathymidine 3 -Phosphate, A-891 6-Azathymidine 5 -Phosphate, A-891 8-Azidocyclic AMP, A-897 3 -Azido-3 -deoxy-5 -thymidylic acid, 9CI, Z-4 Benzyl 2-amino-4,6-0-benzylidene-2-deoxy-a-D-glucopyranoside 3-(dihydrogen phosphate), A-272 8-Bromocyclic AMP, B-53 8-Bromocyclic GMP, B-54 Bucladesine, INN, C-162 Bucladesine sodium, JAN, C-162 Coenzyme A, C-144 Coenzyme II, C-145 Coenzyme I, C-143 Cordycepin 5 -Triphosphate, C-152 Cyclic ADP-ribose, C-I6I Cyclic AMP A-Butanoyl, C-162 Cyclic AMP 2 -Deoxy, C-162 Cyclic AMP, C-162 Cyclic CMP, C-163 Cyclic GMP, C-164 Cyclic TMP, C-165 Cyclic UMP, C-166... 

Syntheses of the adenosine and guanosine 5 -phosphoroazidates (622) and (613), which were required as affinity labels, of P -di([ C]adenosine-5 )penta-phosphate, an inhibitor of adenylate kinase (E.C. 2.7.4.3), and, by improved procedures, of 3 -deoxyadenosine (cordycepin) 5 -triphosphate have been reported. 2 -Deoxy-2 -deuterio-adenosine (276) (see p. 100) and its 2 -epimer have been converted into the corresponding 3, 5 -phosphates, whose conformers were examined by H n.m.r. spectroscopy." ... 

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

The 3 -end labeling is typically carried out using terminal deoxynucleotidyltrans-ferase in the presence of P- or S-labeled ddNTP, 3 -deoxy-ATP (cordycepin triphosphate), or rATP. (Note For most of the procedures involving radiolabeling, nucleotides labeled with should be considered as a preferred substitute.)... 

Various drugs inhibit chain elongation. Cordycepin is converted to a 5 -triphosphate form and then acts as a substrate analogue, blocking chain elongation. 

Apparently cordycepin is converted to its 5 -triphosphate and incorporated into the growing RNA chain. This chain containing cordycepin now lacks a 3 -OH group hence, RNA synthesis is terminated. 

Figure 1-3 shows a number of nucleoside antibiotics which contain adenine and an unusual sugar at the 9-position. Cordycepin (3 -deoxy-adenosine) is a cytostatic agent and is converted to the 5 -mono-, di-, and triphosphate derivatives in mouse tumor cells. Cordyceps militaris, the organism which produces cordycepin, also produces a related analogue with antitumor activity, 3 -amino-3 -deoxyadenosine this compound is also metabolized by way of phosphate derivatives. The angustmycins, psicofuranine and decoyinine, are, respectively, the 9-j3-D-psicofuranosyl... 

---