Tandem activated caged galactoside prodrugs: advancing beyond single galactosidase dependence.

ABSTRACT: β-Galactoside prodrugs, activated by β-galactosidase (β-gal) highly expressed in some cancer cells, have been explored as anticancer agents for three decades. However, the distribution of β-gal lacks sufficient specificity to ensure precise drug release at cancer sites. By utilizing the highly stringent substrate specificity of β-gal, we chose the naturally occurring hydroxyl group of galactose as a prodrug modification site and developed a new class of tandem activated caged galactoside (TACG) prodrugs that require an additional trigger for more controlled on-demand drug release. We demonstrated that attaching various masking groups to the 6-hydroxyl group of galactose renders the galactosides resistant to β-gal hydrolysis. Focusing on the photosensitive mask 4,5-dimethoxy-2-nitrobenzyl (

SUBMITTER: Tan Y 

PROVIDER: S-EPMC11932646 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature