Bt2-Ins(3456)P4 / PM

Bt2-Ins(3,4,5,6)P4/PM is a membrane-permeant, bioactivatable derivative of myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), an intracellular regulator of chloride transport.

The negatively charged phosphate groups are masked by propionoxymethyl (PM) ester groups, while additional butyryl ester groups increase lipophilicity and facilitate cellular uptake. Following entry into cells, intracellular esterases cleave the ester groups, enabling intracellular delivery of Ins(3,4,5,6)P4.

Ins(3,4,5,6)P4 has been shown to regulate Ca²⁺-dependent chloride conductance and epithelial chloride secretion. Membrane-permeant Ins(3,4,5,6)P4 derivatives have been used to investigate these processes in intact cells. Bt2-Ins(3,4,5,6)P4/PM has also been used directly in studies demonstrating regulation of ClC-3 chloride channels, including endosomal Cl⁻ transport.

Damit können wir die bisherige Aussage „chloride secretion modulator“ wissenschaftlich wesentlich besser ausbauen. Die biologische Funktion ist hier ungewöhnlich gut belegt: Die klassische Nature-Arbeit identifizierte Ins(3,4,5,6)P4 als Regulator der Cl⁻-Sekretion und verwendete bereits einen synthetischen membrane-permeanten Ester.

References:

Vajanaphanich M. et al., Nature 1994, 371, 711–714. DOI: 10.1038/371711a0

Xie W. et al., Journal of Biological Chemistry 1996, 271, 14092–14097. DOI: 10.1074/jbc.271.24.14092

Mitchell J. et al., Current Biology 2008, 18, 1600–1605. DOI: 10.1016/j.cub.2008.08.073