270925-65-0Relevant articles and documents
An HIV reverse transcriptase-selective nucleoside chain terminator
Fraley, Andrew W.,Chen, Dongli,Johnson, Kenneth,McLaughlin, Larry W.
, p. 616 - 617 (2003)
The synthesis of a 2-,3-dideoxynucleoside cytidine analogue, but one that lacks the O2-carbonyl, is described from 2-aminopyridine in an overall yield of 60%. The synthesis of the 2-pyridone C-nucleoside relies upon the use of a Heck-type coupling between an appropriately protected sugar glycal and the 5-iodo derivative of 2-aminopyridone. Upon conversion of the dideoxynucleoside to the corresponding 5-triphosphate, the analogue ddNTP is observed to be a reasonable substrate with HIV reverse transcriptase (for a template dG residue), but is not a substrate for calf thymus DNA polymerase α or for human DNA polymerase β. With the human mitochondrial DNA polymerase the analogue functions as a poor substrate. The observed polymerase selectivities appear to arise from the absence of the O2-carbonyl, which either results in a destabilized Watson-Crick base pair or represents a critical contact for some polymerases. Copyright
