124029-65-8Relevant articles and documents
Biologically Useful Chelators That Take Up Ca(2+) upon Illumination
Adams, S. R.,Kao, J. P. Y.,Tsien, R. Y.
, p. 7957 - 7968 (2007/10/02)
Two approaches were explored toward the goal of synthesizing physiologically useful Ca(2+)-selective chelators whose Ca(2+) affinities increase markedly upon photolysis.In the first approach, the known Ca(2+)-selective chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) was masked with a variety of photoremovable protecting groups on one of its four carboxyl groups, reducing its affinity for Ca(2+) to ca. 1E5 M-1.Upon irradiation around 356 nm, free chelator with an affinity constant ca. 1E7 M-1 was regenerated but with very low quantumefficiencies (-1.Photochemical rearrangement of the diazoacetyl group converted it into an electron-donating carboxymethyl group, causing the Ca(2+) affinity to increase 30-fold to 1.4E7 M-1.The photolysis of Ca(2+)-free diazo-2 had a quantum efficiency with 365-nm light (λmax 370 nm, ε ca. 22000 M-1cm-1) of ca. 0.03 and generated the high-affinity chelator with rate constants of 2300 s-1 after a flash.Ca(2+) was then bound with association and dissociation rate constants of 8.0E8 M-1s-1 and 58 s-1, respectively.Diazo-2 was incorporated into rat fibroblasts either by microinjection or by incubation as the membrane-permeable, enzymatically labile tetrakis(acetoxymethyl) ester and, when flash-photolyzed, caused a drop in intracellular free to or below resting values of ca. 1E-7 M.An even larger increase in affinity(1600-fold) was obtained by substituting both phenyl rings of BAPTA with diazoacetyl substituents.Therefore, these chelators can be used to generate controlled fast decrements in intracellular free to mimic or ablate a host of important cellular responses, especially in nerve and muscle.
