Modified Nucleoside 5′-Triphosphonates as a New Type of Antiviral Agents

An Improved Method for the Synthesis of Nucleoside Triphosphate Analogues

“…Mechanistic probes to investigate the roles of phosphate transfer in biological systems are of importance in elucidating the mechanisms of fundamental enzymecatalyzed processes involving primary and secondary metabolism. 1 Non-hydrolyzable nucleotide analogues that are isosteric and isoelectronic with nucleoside triphosphates are examples of analogues that have been used successfully to probe phosphoryl transfer in enzymecatalyzed processes [2][3][4][5][6][7] and receptor specificity. [8][9][10][11] Recently, such halophosphonate analogues have been shown to improve the physiological half-lives of effective HIV reverse-transcriptase inhibitors.…”

“…Mechanistic probes to investigate the roles of phosphate transfer in biological systems are of importance in elucidating the mechanisms of fundamental enzyme-catalyzed processes involving primary and secondary metabolism . Non-hydrolyzable nucleotide analogues that are isosteric and isoelectronic with nucleoside triphosphates are examples of analogues that have been used successfully to probe phosphoryl transfer in enzyme-catalyzed processes − and receptor specificity. − Recently, such halophosphonate analogues have been shown to improve the physiological half-lives of effective HIV reverse-transcriptase inhibitors . The physiochemical benefits associated with halogenation of hydrolysis-inert analogues of pyrophosphate were initially proposed independently by Blackburn and McKenna. , One of the difficulties encountered in exploiting these probes for mechanistic studies is that reported syntheses of non-hydrolyzable nucleotide analogues are lengthy and often low yielding.…”