The present invention relates to disulfide masked prodrug compounds, compositions and methods that are amenable to bioactivation by a reducing agent such as glutathione. Such disulfide based compounds, compositions, and methods can be useful, for example, in providing novel prodrugs for use as therapeutics. The prodrug compounds, compositions and methods of the invention feature a conformationally restricted disulfide phosphotriester moiety to mask anionic charge. The conformationally restricted disulfide phosphotriester moiety can also serve as a scaffold to attach a helper molecule, such as targeting moieties, immunnosuppression moieties, solubility enhancing moieties etc.
