Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Caged compounds: photorelease technology for control of cellular chemistry and physiology

Abstract

Caged compounds are light-sensitive probes that functionally encapsulate biomolecules in an inactive form. Irradiation liberates the trapped molecule, permitting targeted perturbation of a biological process. Uncaging technology and fluorescence microscopy are 'optically orthogonal': the former allows control, and the latter, observation of cellular function. Used in conjunction with other technologies (for example, patch clamp and/or genetics), the light beam becomes a uniquely powerful tool to stimulate a selected biological target in space or time. Here I describe important examples of widely used caged compounds, their design features and synthesis, as well as practical details of how to use them with living cells.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: General strategies caged by either multistep or direct caging.

Katie Ris

Figure 2: Structures and photochemistry of caged compounds.
Figure 3

Katie Ris

Figure 4: Examples of biological applications of caged compounds.

Katie Ris

References

  1. Mayer, G. & Heckel, A. Biologically active molecules with a “light switch”. Angew. Chem. Int. Ed. 45, 4900–4921 (2006).

    CAS  Google Scholar 

  2. Berridge, M.J., Bootman, M.D. & Lipp, P. Calcium-life and death signal. Nature 395, 645–649 (1998).

    CAS  PubMed  Google Scholar 

  3. Adams, S.R., Kao, J.P.Y., Grynkiewicz, G., Minta, A. & Tsien, R.Y. Biologically useful chelators that release Ca2+ upon illumination. J. Am. Chem. Soc. 110, 3212–3220 (1988).

    CAS  Google Scholar 

  4. Ellis-Davies, G.C.R. & Kaplan, J.H. A new class of photolabile chelators for the rapid release of divalent cations: generation of caged Ca and caged Mg. J. Org. Chem. 53, 1966–1969 (1988).

    CAS  Google Scholar 

  5. Ellis-Davies, G.C.R. & Kaplan, J.H. Nitrophenyl-EGTA, a photolabile chelator that selectively binds Ca2+ with high affinity and releases it rapidly upon photolysis. Proc. Natl. Acad. Sci. USA 91, 187–191 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ellis-Davies, G.C.R. Synthesis of photolabile EGTA derivatives. Tetrahedr. Lett. 39, 953–957 (1998).

    CAS  Google Scholar 

  7. Walker, J.W., McCray, J.A. & Hess, G.P. Photolabile protecting groups for an acetylcholine receptor ligand. Synthesis and photochemistry of a new class of o-nitrobenzyl derivatives and their effects on receptor function. Biochemistry 25, 1799–1805 (1986).

    CAS  PubMed  Google Scholar 

  8. Milburn, T. et al. Synthesis, photochemistry and biological activity of a caged photolabile acetylcholine receptor ligand. Biochemistry 28, 49–55 (1989).

    CAS  PubMed  Google Scholar 

  9. Wieboldt, R. et al. Photolabile precursors of glutamate: Synthesis, photochemical properties, activation of glutamate receptors in the microsecond time scale. Proc. Natl. Acad. Sci. USA 91, 8752–8756 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Matsuzaki, M. et al. Dendritic spine morphology is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat. Neurosci. 4, 1086–1092 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Walker, J.W. et al. Kinetics of smooth and skeletal muscle activation by laser pulse photolysis of caged inositol 1,4,5-trisphosphate. Nature 327, 249–252 (1987).

    CAS  PubMed  Google Scholar 

  12. Walker, J.W., Feeney, J. & Trentham, D.R. Photolabile precursors of inositol phosphates. Preparation and properties of 1-(2-nitrophenyl)ethyl esters of myo-inositol 1,4,5-trisphosphate. Biochemistry 28, 3272–3280 (1989).

    CAS  PubMed  Google Scholar 

  13. Kaplan, J.H., Forbush, B. & Hoffman, J.F. Rapid photolytic release of adenosine 5′-triphosphate from a protected analogue: utilization by the Na:K pump of human red blood cell ghosts. Biochemistry 17, 1929–1935 (1978).

    CAS  PubMed  Google Scholar 

  14. Walker, J.H., Reid, G.P., McCray, J.A. & Trentham, D.R. Photolabile 1-(2-nitrophenyl)ethyl phosphate esters of adenine nucleotide analogues. Synthesis and mechanism of photolysis. J. Am. Chem. Soc. 110, 7170–7177 (1988).

    CAS  Google Scholar 

  15. Walker, J.W. et al. Signaling pathways underlying eosinophil cell motility revealed by using caged peptides. Proc. Natl. Acad. Sci. USA 95, 1568–1573 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Rothman, D.M. et al. Caged phosphoproteins. J. Am. Chem. Soc. 127, 846–847 (2005).

    CAS  PubMed  Google Scholar 

  17. Marriott, G. Caged protein conjugates and light-directed generation of protein activity: preparation, photoactivation, and spectroscopic characterization of caged G-actin conjugates. Biochemistry 33, 9092–9097 (1994).

    CAS  PubMed  Google Scholar 

  18. Mendel, D., Elman, J.A. & Schultz, P.G. Construction of light-activated protein-protein interactions. J. Am. Chem. Soc. 113, 2758–2760 (1991).

    CAS  Google Scholar 

  19. Ghosh, M. et al. Cofilin promotes actin polymerization and defines the direction of cell motility. Science 304, 743–746 (2004).

    CAS  PubMed  Google Scholar 

  20. Ando, H., Furuta, T., Tsien, R.Y. & Okamoto, H. Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Nat. Genet. 28, 317–325 (2001).

    CAS  PubMed  Google Scholar 

  21. Monroe, W.T., McQuain, M.M., Chang, M.S., Alexander, J.S. & Haselton, F.R. Targeting expression with light using caged DNA. J. Biol. Chem. 274, 20895–20900 (1999).

    CAS  PubMed  Google Scholar 

  22. Kasai, H. Comparative biology of Ca-dependent exocytosis: implications of kinetic diversity for secretory function. Trends Neurosci. 22, 88–93 (1999).

    CAS  PubMed  Google Scholar 

  23. Judkewitz, B., Roth, A. & Hausser, M. Dendritic enlightenment: using patterned two-photon uncaging to reveal the secrets of the brain's smallest dendrites. Neuron 50, 180–183 (2006).

    CAS  PubMed  Google Scholar 

  24. Pelliccioli, A.P. & Wirz, J. Photoremovable protecting groups: reaction mechanisms and applications. Photochem. Photobiol. Sci. 1, 441–458 (2002).

    PubMed  Google Scholar 

  25. McGall, G.H. et al. The efficiency of light-directed synthesis of DNA arrays on glass substrates. J. Am. Chem. Soc. 119, 5081–5090 (1997).

    CAS  Google Scholar 

  26. McGall, G.H. & Christians, F.C. High-density genechip oligonucleotide probe arrays. Adv. Biochem. Eng. Biotechnol. 77, 22–42 (2002).

    Google Scholar 

  27. Ellis-Davies, G.C.R. Caged Glutamate For Use in the CNS. New Encyclopedia of Neuroscience. (eds., Squire, L., Albright, T., Bloom, F., Gage, F. & Spritzer, N.) (Elsevier, Oxford, in the press).

  28. Gee, K.R., Wieboldt, R. & Hess, G.P. Synthesis and photochemistry of a new photolabile derivative of GABA. J. Am. Chem. Soc. 116, 8366–8367 (1994).

    CAS  Google Scholar 

  29. Molnar, P. & Nadler, J.V. γ-Aminobutyrate, a-carboxy-2-nitrobenzyl ester selectively blocks inhibitory synaptic transmission in rat dentate gyrus. Eur. J. Pharm. 391, 255–262 (2000).

    CAS  Google Scholar 

  30. Engels, J. & Schlaeger, E-J. Synthesis, structure and reactivity of adenosine cyclic 3′,5′-phosphate benzyl triesters. J. Med. Chem. 20, 907–911 (1977).

    CAS  PubMed  Google Scholar 

  31. Dantzig, J.A., Higuchi, H. & Goldman, Y.E. Studies of molecular motors using caged compounds. Methods Enzymol. 291, 307–348 (1998).

    CAS  PubMed  Google Scholar 

  32. Ogden, D. & Khodakhah, K. Intracellular Ca2+ release by InsP3 in cerebellar Purkinje neurones. Acta Physiol. Scan. 157, 381–394 (1996).

    CAS  Google Scholar 

  33. Bamberg, E., Clarke, R.J. & Fendler, K. Electrogenic properties of the Na+,K+-ATPase probed by presteady state and relaxation studies. J. Bionerg. Biomembr. 33, 401–405 (2001).

    CAS  Google Scholar 

  34. Wang, L., Corrie, J.T. & Wootton, J.F. Photolabile precursors of cyclic nucleotides with high aqueous solubility and stability. J. Org. Chem. 67, 3474–3478 (2002).

    CAS  PubMed  Google Scholar 

  35. Thirlwell, H. et al. Kinetics of relaxation from rigor of permeabilized fast-twitch skeletal fibers from the rabbit using a novel caged ATP and apyrase. Biophys. J. 67, 2436–2447 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Geibel, S. et al. P(3)-[2-(4-hydroxyphenyl)-2-oxo]ethyl ATP for the rapid activation of the Na+,K+-ATPase. Biophys. J. 79, 1346–1357 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Kantevari, S., Egger, M., Hoing, C., Niggli, E. & Ellis-Davies, G.C.R. Synthesis and 2-photon photolysis of 6-(ortho-nitroveratryl)-caged IP3 . ChemBioChem 7, 174–180 (2006).

    CAS  PubMed  Google Scholar 

  38. Hagen, V. et al. Highly efficient and ultrafast phototriggers for cAMP and cGMP by using long-wavelength UV/vis-activation. Angew. Chem. Int. Ed. 40, 1045–1048 (2001).

    Google Scholar 

  39. Furuta, T. et al. Bhc-cNMPs as either water-soluble or membrane-permeant photoreleasable cyclic nucleotides for both one- and two-photon excitation. ChemBioChem 5, 1119–1128 (2004).

    CAS  PubMed  Google Scholar 

  40. Li, W., Llopis, J., Whitney, M., Zlokarnik, G. & Tsien, R.Y. Cell-permeant caged InsP3 ester analog shows that Ca2+ spike frequency can optimize gene expression. Nature 392, 936–941 (1998).

    CAS  PubMed  Google Scholar 

  41. Ellis-Davies, G.C.R. Development and application of calcium cages. Meth. Enzymol. 360A, 226–238 (2003).

    Google Scholar 

  42. Adams, S.R., Lev-Ram, V. & Tsien, R.Y. A new caged Ca2+, azid-1, is far more photosensitive than nitrobenzyl-based chelators. Chem. Biol. 4, 867–878 (1997).

    CAS  PubMed  Google Scholar 

  43. Momotake, A., Lindegger, N., Niggli, N., Barsotti, R.J. & Ellis-Davies, G.C.R. The nitrodibenzofuran chromophore-a new caging group for ultra efficient photolysis in living cells. Nat. Methods 3, 35–40 (2006).

    CAS  PubMed  Google Scholar 

  44. Neher, E. Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron 20, 389–399 (1998).

    CAS  PubMed  Google Scholar 

  45. Rettig, J. & Neher, E. Emerging roles of presynaptic proteins in Ca2+-triggered exocytosis. Science 298, 781–785 (2002).

    CAS  PubMed  Google Scholar 

  46. Marriott, G., Roy, P. & Jakobson, K. Preparation and light-directed activation of caged proteins. Methods Enzymol. 360, 274–288 (2003).

    CAS  PubMed  Google Scholar 

  47. Chang, C., Fernandez, T., Panchal, R. & Bayley, H. Caged catalytic subunit of cAMP-dependent protein kinase. J. Am. Chem. Soc. 120, 7661–7662 (1998).

    CAS  Google Scholar 

  48. Curley, K. & Lawrence, D.S. Photoactivation of a signal transduction pathway in living cells. J. Am. Chem. Soc. 120, 8573–8574 (1998).

    CAS  Google Scholar 

  49. Petersson, E.J., Brandt, G.S., Zacharias, N.M., Dougherty, D.A. & Lester, H.A. Caging proteins through unnatural amino acid mutagenesis. Methods Enzymol. 360, 258–273 (2003).

    CAS  PubMed  Google Scholar 

  50. Muralidharan, V. & Muir, T.W. Protein ligation: an enabling technology for the biophysical analysis of proteins. Nat. Methods 3, 429–438 (2006).

    CAS  PubMed  Google Scholar 

  51. Hahn, M.E. & Muir, T.W. Photocontrol of Smad2, a multiphosphorylated cell-signaling protein, through caging of activating phosphoserines. Angew. Chem. Int. Ed. 43, 5800–5803 (2004).

    CAS  Google Scholar 

  52. Vazquez, M.E., Nitz, M., Stehn, J., Yaffe, M.B. & Imperiali, B. Fluorescent caged phosphoserine peptides as probes to investigate phosphorylation-dependent protein associations. J. Am. Chem. Soc. 125, 10150–10151 (2003).

    CAS  PubMed  Google Scholar 

  53. Nguyen, A., Rothman, D.M., Stehn, J., Imperiali, B. & Yaffe, M.B. Caged phosphopeptides reveal a temporal role for 14–3-3 in G1 arrest and S-phase checkpoint function. Nat. Biotechnol. 22, 993–1000 (2004).

    CAS  PubMed  Google Scholar 

  54. Wood, J.S., Koszelak, M., Liu, J. & Lawrence, D.S. A caged protein kinase inhibitor. J. Am. Chem. Soc. 120, 7145–7146 (1998).

    CAS  Google Scholar 

  55. Bosques, C.J. & Imperiali, B. Photolytic control of peptide self-assembly. J. Am. Chem. Soc. 125, 7530–7531 (2003).

    CAS  PubMed  Google Scholar 

  56. Ottl, J., Gariel, D. & Marriott, G. Preparation and photoactivation of caged fluorophores and caged proteins using a new class of heterobifunctional, photocleavable cross-linking reagents. Bioconjug. Chem. 9, 143–151 (1998).

    CAS  PubMed  Google Scholar 

  57. Ando, H. & Okamoto, H. Practical procedures for ectopic induction of gene expression in zebrafish embryos using Bhc-diazo-caged mRNA. Methods Cell Sci. 25, 25–31 (2003).

    CAS  PubMed  Google Scholar 

  58. Okamoto, H., Hirate, Y. & Ando, H. Systematic identification of factors in zebrafish regulating the early midbrain and cerebellar development by ordered differential display and caged mRNA technology. Front. Biosci. 9, 93–99 (2004).

    CAS  PubMed  Google Scholar 

  59. Ando, H. et al. Lhx2 mediates the activity of Six3 in zebrafish forebrain growth. Dev. Biol. 287, 456–468 (2005).

    CAS  PubMed  Google Scholar 

  60. Khan, S. et al. Excitatory signaling in bacterial probed by caged chemoeffectors. Biophys. J. 65, 2368–2382 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Namiki, S., Arai, T. & Fujimori, K. High-performance caged nitric oxide: a new molecular design, synthesis and photochemical reaction. J. Am. Chem. Soc. 119, 2840–3841 (1997).

    Google Scholar 

  62. Goeldner, M. & Givens, R., eds. Dynamic Studies in Biology. (Wiley-VCH, Weinheim, Germany 2005)

    Google Scholar 

  63. Furuta, T. et al. Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two-photon photolysis. Proc. Natl. Acad. Sci. USA 96, 1193–1200 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Papageorgiou, G., Ogden, D.C., Barth, A. & Corrie, J.T. Photorelease of carboxylic acids from 1-acyl-7-nitroindolines in aqueous solution: rapid and efficient photorelease of L-glutamate. J. AM. Chem. Soc. 121, 6503–6504 (1999).

    CAS  Google Scholar 

  65. Wettermark, G. Photochromism of o-nitrotoluenes. Nature 194, 677 (1962).

    CAS  Google Scholar 

  66. Gaplovsky, M. et al. Photochemical reaction mechanisms of 2-nitrobenzyl compounds: 2-nitrobenzyl alcohols form 2-nitroso hydrates by dual proton transfer. Photochem. Photobiol. Sci. 4, 33–42 (2005).

    CAS  PubMed  Google Scholar 

  67. Hirayama, Y., Iwamura, M. & Furuta, T. Design, synthesis and photochemical properties of caged bile acids. Bioorg. Med. Chem. Lett. 13, 905–908 (2003).

    CAS  PubMed  Google Scholar 

  68. Havinga, E., De Jongh, R.O. & Dorst, W. Photochemical acceleration of the hydrolysis of nitrophenyl phosphates and nitrophenyl sulfates. Recl. Trav. Chim. Pays-Bas. 75, 378–383 (1956).

    CAS  Google Scholar 

  69. Heidelberger, R., Heinemann, C., Neher, E. & Matthews, G. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371, 513–515 (1994).

    CAS  PubMed  Google Scholar 

  70. Gillis, K.D., Mossner, R. & Neher, E. Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules. Neuron 16, 1209–1220 (1996).

    CAS  PubMed  Google Scholar 

  71. Xu, T., Naraghi, M., Kang, H. & Neher, E. Kinetic studies of Ca binding and Ca clearance in the cytosol of adrenal chromaffin cells. Biophys. J. 73, 532–545 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Beutner, D., Voets, T., Neher, E. & Moser, T. Calcium dependence of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse. Neuron 29, 681–690 (2001).

    CAS  PubMed  Google Scholar 

  73. Dzeja, C. Hagen, V. Kaupp, U.B. & Frings, S. Ca2+ permeation in cyclic nucleotide-gated channels. EMBO J. 18, 131–144 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Rapp, G. et al. Lasers and flashlamps in research on the mechanism of muscle contraction. Ber. Bunsenges. Phys. Chem 93, 410–415 (1989).

    Google Scholar 

  75. Gomez, T.M., Robles, E., Poo, M. & Spitzer, N.C. Filopodial calcium transients promote substrate-dependent growth cone turning. Science 291, 1983–1988 (2001).

    CAS  PubMed  Google Scholar 

  76. Fellin, T. et al. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43, 729–743 (2005).

    Google Scholar 

  77. Zimmermann, B., Ellis-Davies, G.C.R., Kaplan, J.H., Somlyo, A.V. & Somlyo, A.P. Kinetics of contractions initiated by photolysis of caged calcium and caged ATP in smooth muscle. J. Biol. Chem. 270, 23966–23874 (1995).

    CAS  PubMed  Google Scholar 

  78. Denk, W. Two-photon scanning photochemical microscopy: mapping ligand-gated ion channel distributions. Proc. Natl. Acad. Sci. USA 91, 6629–6633 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Neher, E. & Zucker, R.S. Multiple calcium-dependent processes related to secretion in bovine chromaffin cells. Neuron 10, 21–30 (1993).

    CAS  PubMed  Google Scholar 

  80. Thomas, P., Wong, P.G., Lee, A. & Almers, W. W. A low affinity Ca receptor controls the final steps in peptide secretion from pituitary melanotrophs. Neuron 11, 93–104 (1993).

    CAS  PubMed  Google Scholar 

  81. Kasai, H. et al. Two components of exocytosis and endocytosis in phaeochromocytoma cells studied using caged Ca compounds. J. Physiol. 494, 53–65 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Schneggenburger, R. & Neher, E. Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406, 889–893 (2000).

    CAS  PubMed  Google Scholar 

  83. Bollmann, J.H. Sakmann, B. & Borst, J.G.G. Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289, 953–957 (2000).

    CAS  PubMed  Google Scholar 

  84. Khodakhah, K. & Ogden, D. Functional heterogeneity of calcium release by inositol trisphosphate in single Purkinje neurones, cultured cerebellar astrocytes, and peripheral tissues. Proc. Natl. Acad. Sci. USA 90, 4976–4980 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Kaplan, J.H. & Ellis-Davies, G.C.R. Photolabile chelators for the rapid photorelease of divalent cations. Proc. Natl. Acad. Sci. USA 85, 6571–6575 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Gomez, T.M. & Spitzer, N.C. In vivo regulation of axon and pathfinding by growth cone calcium transients. Nature 397, 350–355 (1999).

    CAS  PubMed  Google Scholar 

  87. Finch, E.A. & Augustine, G.J. Local calcium signaling by IP3 in Purkinje cell dendrites. Nature 396, 753–756 (1998).

    CAS  PubMed  Google Scholar 

  88. Smith, M.A., Ellis-Davies, G.C.R. & Magee, J.C. Synaptic mechanisms of the distance-dependent scaling of Schaffer collateral synapses in CA1 pyramidal neurons. J. Physiol. 548, 245–258 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Carter, A.G. & Sabatini, B.L. State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons. Neuron 44, 483–493 (2004).

    CAS  PubMed  Google Scholar 

  90. Sobczyk, A., Scheuss, V. & Svoboda, K. NMDA Receptor subunit-dependent [Ca2+] signaling in individual hippocampal dendritic spines. J. Neurosci. 25, 6037–6046 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Béïque, J.C., Da-Ting Lin, D.T., Kang, M.G., Aizawa, H., Takamiya, K. & and Huganir, R.L. Synapse-specific regulation of AMPA receptor function by PSD-95. Proc. Natl. Acad. Sci. USA 103, 19535–19540 (2006).

    PubMed  PubMed Central  Google Scholar 

  92. Katz, B. & Miledi, R. The effect of calcium on acetylcholine release from motor nerve terminals. Proc. Roy. Soc. B. Biol. Sci. 161, 496–503 (1965).

    CAS  Google Scholar 

  93. Ellis-Davies, G.C.R., Momotake, M., Paukert, M., Kasai, H. & Bergles, D.W. 4-carboxymethoxy-5,7-dinitroindolinyl-Glu: an improved caged glutamate for expeditious ultraviolet and 2-photon photolysis in brain slices. J. Neurosci. 27, 6601–6604 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Banghart, M., Borges, K., Isacoff, E., Trauner, D. & Kramer, R.H. Light-activated ion channels for remote control of neuronal firing. Nat. Neurosci. 7, 1381–1386 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Kumita, J.R., Smart, O.S. & Woolley, G.A. Photo-control of helix content in a short peptide. Proc. Natl. Acad. Sci. USA 97, 3803–3808 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Shingyoji, C., Higuchi, H., Yoshimura, M., Katayama, E. & Yanagida, T. Dynein arms are oscillating force generators. Nature 393, 711–714 (1998).

    CAS  PubMed  Google Scholar 

  97. Denk, W., Stricker, J.H. & Webb, W.W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    CAS  PubMed  Google Scholar 

  98. Brown, E.B. et al. Photolysis of caged calcium in femtoliter volumes using two-photon excitation. Biophys. J. 76, 489–499 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Huang, Y.H., Sinha, S.R., Fedoryak, O.D., Ellis-Davies, G.C.R. & Bergles, D.E. Synthesis and characterization of MNI-D-aspartate, a caged compound for selective activation of glutamate transporters and NMDA receptors in brain tissue. Biochemistry 44, 3316–3326 (2005).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Ellis-Davies laboratory is supported by grants from the US National Institutes of Health GM53395, GM65473 and MH0717505.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Graham C R Ellis-Davies.

Ethics declarations

Competing interests

G.C.R.E.-D. has patents on NP-EGTA and DM-nitrophen, and preliminary patent declarations have been filed on NDBF and CDNI.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ellis-Davies, G. Caged compounds: photorelease technology for control of cellular chemistry and physiology. Nat Methods 4, 619–628 (2007). https://doi.org/10.1038/nmeth1072

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmeth1072

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing