Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Patent
1993-11-09
1995-08-29
Dees, Josee G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
556131, 556148, 562434, 562489, 562565, 562568, 564441, 564442, 564443, 568 44, 568 45, 568 46, 568 54, 568 55, 568 56, 568584, 568587, 568588, 568593, 568608, 568630, 568651, 568656, 568662, 568663, 2041574, C07F 1300, C07F 300, C07C22900
Patent
active
054461863
ABSTRACT:
The synthesis and compound of a new caged calcium which is an ortho-nitrophenyl derivative of EGTA and various intermediates. It is synthesized in ten steps and 24% overall yield. The photosensitive chelator, nitrophenyl-EGTA, has a K.sub.d for Ca.sup.2+ of 80 nM and for Mg.sup.2+ of 8.8 mM. Upon exposure to ultra-violet light (in the region of 350 nm), the chelator is cleaved, yielding iminodiacetic acid photoproducts with known low Ca-affinity (K.sub.d =1 mM). The quantum yield of photolysis of nitrophenyl-EGTA in the presence of Ca.sup.a+ is 0.23 and in the absence of Ca.sup.2+ is 0.20. In experiments with chemically skinned skeletal muscle fibers, a fully relaxed fiber equilibrated with nitrophenyl-EGTA:Ca.sup.2+ complex, in the presence of physiological [Mg.sup.2+ ] (i.e. 1.0 mM), produced maximal contraction after a single flash from a frequency doubled ruby laser (347 nm). Half-maximal tension was achieved in 18 ms at 15.degree. C. Nitrophenyl-EGTA provides a new tool for the investigation of the mechanism of Ca.sup.2+ -dependent physiological processes, since under conditions of normal intracellular Ca.sup.2+ and Mg.sup.2+ ions, only Ca.sup.2+ ions are bound by the photolabile chelator and on illumination are released rapidly and in high photochemical yield.
REFERENCES:
patent: 4981985 (1991-01-01), Kaplan et al.
Kaplan, J. H. (1990 Annu. Rev. Physiol. 52, 897-914.
Adams, S. R., Kao, J. P. Y., Grynkiewicz, G., Minta, A., & Tsien, R. Y. (1988) J. Am. Chem. Soc. 110, 3212-3220.
Ellis-Davies, G. C. R., & Kaplan, J. H. (1988) J. Org. Chem. 53, 1966-1969.
Kaplan, J. H., & Ellis-Davies, G. C. R. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 6571-6575.
Morad, M., Davies, N. W., Kaplan, J. H., & Lux, H. D. (1988) Science 241, 842-844.
Niggli, E. and Lipp, P. (1993) Biophys J. 55 400a.
Naebauer, M., Ellis-Davies, G. C. R., Kaplan, J. H. & Morad, M. (1989) Am. J. Physiol. 256, H916-20.
Delaney, K. R., & Zucker, R. S. (1990) J. Physiol. 426, 473-498.
Rapp, G., Poole, K. J. V., Maeda, Y., Kaplan, J. H., Ellis-Davies, G. C. R., McCray, J. A., & Goody, R. S. (1990) Bunseges. Phys. Chem 93, 410-424.
Iino M, & Endo, M (1992) Nature 360, 76-78.
Allen, T. S., Barsotii, R. J., Ellis-Davies, G. C. R., Kaplan, J. H. Goldman, Y. E., Martyn, D. A., & Gordon, A. M. (1993) Biophys. J. 64, 135a.
Neher, E. & Zucker, R. S. (1993) Neuron 10, 21-30.
Thomas, P., Wong, J. G., & Almers, W. EMBO J. 12, 303-306. (1993).
Johnson, B. D. & Byerly, L. (1993) J. Physiol. 462, 321-347.
Zucker, R. S. (1992) Cell Calcium 13, 29-40.
Kaplan, J. H., Forbush, B., & Hoffman, J. F. (1978) Biochemistry 17, 1929-1935.
Minta, A., Kao, J. P. Y., & Tisen, R. Y. (1989) J. Biol. Chem. 264, 8171-8178.
McCray, J. A., Fidler-Lim, N., Ellis-Davies, G. C. R., & Kaplan, J. H. (1992) Biochemistry 31, 8856-8861.
Zucker, R. S. (1993) Cell Calcium 14, 87-100.
Harkins, A. B., Kurebayashi, N., & Baylor, S. M. (1993) Biophys. J. 64, 241a.
Konishi, M. & Baylor, S. M. (1991) J. Gen Physiol. 97, 245-270.
Pape, P. C., Konishi, M., Hollingworth, S., & Baylor, S. M. (1990) J. Gen. Phys. 96, 493-516.
Goldman, Y. G., Hibberd, M. G., & Trentham, D. R. (1984) J. Physiol. 354, 701-705.
Ellis-Davies Graham C. R.
Kaplan Jack H.
Dees Josee G.
Nazario-Gonzalez Porfirio
LandOfFree
Structure and synthesis of nitrophenyl-EGTA, a caged calcium, in does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Structure and synthesis of nitrophenyl-EGTA, a caged calcium, in, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Structure and synthesis of nitrophenyl-EGTA, a caged calcium, in will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1820443