New Photoreactive N⁴-Substituted dCTP Analogues: Preparation, Photochemical Characteristics, and Substrate Properties in HIV-1 Reverse Transcriptase-Catalyzed DNA Synthesis

Photochemical characteristics and substrate properties of four newly synthesized dCTP analogues: N⁴-[2-(2-nitro-5-azidobenzoylamino)ethyl]-, N⁴-[2-(4-azidotetrafluorobenzylideneaminooxymethylcarbamoyl)ethyl]-, N⁴-[4-(4-azidotetrafluorobenzylideneaminooxy)butyloxy]-, and N⁴-[4-(4-azidotetrafluorobenzylidene hydrazinocarbonyl)butylcarbamoyl]-, and N ⁴-[4-(4-azidotetrafluorobenzylideneaminooxy)butyloxy]-2′- deoxycytidine 5′-triphosphates as well as those of the earlier described N⁴-[2-(4-azidotetrafluorobenzoylamino)ethyl]- and 5-[E-3-(4-azidotetrafluorobenzoylamino)-1-propenyl)]-2′-deoxycytidine 5′-triphosphates were compared. When being irradiated with UV light at a wavelength of 303-313 nm, the new analogues demonstrated greater than 10-fold higher photoactivity as compared with the old compounds. The first three new compounds were utilized by HIV-1 reverse transcriptase as dCTP and dTTP, while the last derivative was recognized only as dTTP. Once incorporated into the primer 3′-terminus, none of the analogues synthesized terminated further primer elongation with natural triphosphates.