Deoxyadenosine pentostatin actions

Pentostatin (deoxycoformycin Fig. 4) is a purine isolated from cultures of Streptomyces antibioticus. Its mode of action involves inhibition of adenosine deaminase, which plays a key role in purine salvage pathways and DNA synthesis. As a consequence, deoxyadenosine triphosphate (dATP) is accumulated, which is highly toxic to lymphocytes. This is associated with augmented susceptibility to apoptosis, particularly in T cells. 

Pentostatin (Fig. 42.25) is a ring-expanded purine ribonuoleoside that inhibits adenosine deaminase and is used in the treatment of hairy cell leukemia. The elevated levels of deoxyadenosine triphosphate that result from inhibition of this degradative enzyme inhibit the action of ribonucleotide reductase (the enzyme that converts ribose diphosphate to deoxyribose diphosphate), thus halting DNA synthesis within the tumor cell. 

Pentostatin also belongs in the antimetabolite category although its mechanism of action is totally different from that of other antimetabolites. Pentostatin is a natural product isolated from the fermentation broth of Streptomyces. It is an example of a dmg which is a transition-state analogue which is believed to mimic the transition state of 2-deoxyadenosine when it is being deamidated (Fig. 21.12). The conversion of 2-deoxyadenosine into 2-deoxyinosine is an important metabolic step in controlling DNA synthesis. If the conversion does not occur, 2-deoxyadenosine accumulates and is converted into its triphosphate (dATP), which is a potent... 

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See also in sourсe #XX -- [ , ]

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