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Updated: Jun 8, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
Published on: April 3, 2014
Prodrugs of aza nucleosides based on proton transfer reaction
1Faculty of Pharmacy, Al-Quds University, Jerusalem, Palestine. dr_karaman@yahoo.com
Abstract:
DFT calculation results for intramolecular proton transfer reactions in Kirby's enzyme models 1-7 reveal that the reaction rate is quite responsive to geometric disposition, especially to distance between the two reactive centers, r (GM), and the angle of attack, α (the hydrogen bonding angle). Hence, the study on the systems reported herein could provide a good basis for designing aza nucleoside prodrug systems that are less hydrophilic than their parental drugs and can be used, in different dosage forms, to release the parent drug in a controlled manner. For example, based on the calculated log EM, the cleavage process for prodrug 1ProD is predicted to be about 10¹⁰ times faster than that for prodrug 7ProD and about 10⁴ times faster than prodrug 3ProD: rate( 1ProD ) > rate( 3ProD ) > rate( 7ProD ). Hence, the rate by which the prodrug releases the aza nucleoside drug can be determined according to the structural features of the linker (Kirby's enzyme model).
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