Abstract
Synthetic nucleosides, designed to mimic naturally occurring nucleosides, are important antiviral and anticancer chemotherapeutic agents. However, nucleosides are not active as such and need to be metabolized, step by step, to their corresponding active nucleoside triphosphates (NTPs). This is mediated by phosphorylating enzymes, mainly host cellular kinases with strong specificity for their substrates; in many cases, this specificity prevents efficient conversion into the NTPs. To circumvent this metabolic handicap, successful nucleo(s/t)ide prodrugs have been developed as a valuable concept in the design of effective drugs. The unique concept of the TriPPPro approach, developed by Chris Meier and colleagues, is a powerful tool for the intracellular delivery of active NTPs, bypassing all the phosphorylation steps required by nucleosides to yield the active NTP metabolites. This concept is illustrated herein with general examples.
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Citations
May 8, 2020·Angewandte Chemie·Chenglong ZhaoChris Meier
Oct 23, 2020·ChemMedChem·Chenglong ZhaoChris Meier
May 1, 2021·RSC Chemical Biology·Adeline EspinasseErin E Carlson
Nov 2, 2021·Chemical & Pharmaceutical Bulletin·Takato SakuradaYosuke Taniguchi