Abstract
A summary of the most recent advances to the design of pro-nucleotides will be presented. Approaches that have been designed to be activated by enzymes such as carboxyesterases [bis(POM)-, bis(POC)-, bis (SATE)-, bis (AB) phosphotriesters and the arylphosphoramidates] or by reductases [bis(SDTE) approach] will be discussed as well as the amino acids phosporamidate diester concept with its still unknown delivery mechanism and the cycloSal approach that releases the nucleotides by an induced tandem reaction.

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