Evaluation of a 7-Methoxycoumarin-3-carboxylic Acid Ester Derivative as a Fluorescent, Cell-Cleavable, Phosphonate Protecting Group.

ABSTRACT: Cell-cleavable protecting groups often enhance cellular delivery of species that are charged at physiological pH. Although several phosphonate protecting groups have achieved clinical success, it remains difficult to use these prodrugs in live cells to clarify biological mechanisms. Here, we present a strategy that uses a 7-methoxycoumarin-3-carboxylic acid ester as a fluorescent protecting group. This strategy was applied to synthesis of an (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) analogue to assess cellular uptake and human Vγ9Vδ2 T cell activation. The fluorescent ester displayed low cellular toxicity (IC50 >100 μm) and strong T cell activation (EC50 =0.018 μm) relative to the unprotected anion (EC50 =23 μm). The coumarin-derived analogue allowed no-wash analysis of biologi

SUBMITTER: Wiemer AJ 

PROVIDER: S-EPMC4746711 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature