Pronucleotides: Toward the in vivo delivery of antiviral and anticancer nucleotides

To overcome the many hurdles preventing the use of antiviral and anticancer nucleosides as therapeutics, the development of a prodrug methodology (i.e ., pronucleotide) for the in vivo delivery of nucleotides has been proposed as a solution. The ideal pronucleotide should be non-toxic, stable in plas ma and blood, capable of being i.v. and/or orally dosed, and intracellularl y convertible to the corresponding nucleotide. Although this goal has yet t o be achieved, many clever and imaginative pronucleotide approaches have be en developed, which are likely to be important pharmacological tools. This review will discuss the major advances and future directions of the emergin g field of antiviral and anticancer pronucleotide design and development. ( C) 2000 John Wiley & Sons.