Indoxyl-glucosides bearing tethers for enzymatically triggered cross-linking

Abstract

Indoxyl-glucosides upon treatment with β-glucosidase under physiological conditions are well known to afford the corresponding indigoid dye via oxidative dimerization. Here, seven indoxyl-glucoside monomers (and 13 indoxyl intermediates) have been prepared wherein a handle is attached to the indoxyl moiety. The handles include azido, hydroxy, or biotin positioned at the terminus of a short oligoethylene glycol (PEG) chain. Three of the indoxyl-glucoside target compounds are N-alkylated with a carboxymethyl unit. The yields of indigoid upon glucosidase treatment were approximately quantitative for the unalkylated compounds versus 1/4–1/3 of that for the N-carboxymethyl analogues. Hybrid joining reactions from two indoxyl-glucosides, which form three products, also were explored. A bis(indoxyl-glucoside)-tyrosine compound has been prepared as a prototype for studies of molecular brachytherapy. The tyrosine moiety has been iodinated under conditions that mirror those for radioiodination. In general, the well-known chromogenic readout afforded by indigoid formation and the ability to join two entities suggests numerous applications in bioorganic chemistry.