Deoxyadenosine family: improved synthesis, DNA damage and repair, analogs as drugs

Abstract

AbstractImproved synthesis of 2′-deoxyadenosine using Escherichia coli overexpressing some enzymes and gram-scale chemical synthesis of 2′-deoxynucleoside 5′-triphosphates reported recently are described in this review. Other topics include DNA damage induced by chromium(VI), Fenton chemistry, photoinduction with lumazine, or by ultrasound in neutral solution; 8,5′-cyclo-2′-deoxyadenosine isomers as potential biomarkers; and a recapitulation of purine 5′,8-cyclonucleoside studies. The mutagenicities of some products generated by oxidizing 2′-deoxyadenosine 5′-triphosphate, nucleotide pool sanitization, and translesion synthesis are also reviewed. Characterizing cross-linking between nucleosides in opposite strands of DNA and endonuclease V-mediated deoxyinosine excision repair are discussed. The use of purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias is reviewed. Some analogs at the C8 position induced delayed polymerization arrest during HIV-1 reverse transcription. The susceptibility of clinically metronidazole-resistant Trichomonas vaginalis to two analogs, toyocamycin and 2-fluoro-2′-deoxyadenosine, were tested in vitro. GS-9148, a dAMP analog, was translocated to the priming site in a complex with reverse transcriptase and double-stranded DNA to gain insight into the mechanism of reverse transcriptase inhibition.