Abstact
A reaction of high-temperature solid-phase catalytic isotope exchange (HSCIE) was studied for the preparation of tritium- and deuterium-labeled ligands of glutamate and dopamine receptors. Tritium-labeled (5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclopenten-5,1-imine ([G-3H]MK-801) and R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetraline ([G-3H]-7-OH-DPAT) were obtained with a specific activity of 210 and 120 Ci/mol, respectively. The isotopomeric distribution of deuterium-labeled ligands was studied using time-of-flight mass-spectrometer MX 5310 (ESI-o-TOF) with electrospray and orthogonal ion injection. Mean deuterium incorporation per ligand molecule was 11.09 and 3.21 atoms for [G-3H]MK-801 and [G-3H]-7-OH-DPAT, respectively. The isotope label was shown to be distributed all over the ligand molecule. The radioreceptor binding of tritium-labeled ligands [G-3H]MK-801 and [G-3H]-7-OH-DPAT was analyzed using the brain structure of Vistar rats. It was demonstrated that [G-3H]MK-801 specifically binds to hippocampus membranes with K d 8.3 ± 1.4 nM, B max being 3345 ± 300 fmol/mg protein. The [G-3H]-7-OH-DPAT ligand specifically binds to rat striatum membranes with K d 10.01 ± 0.91 nM and B max 125 ± 4.5 fmol/mg protein. It was concluded that the HSCIE reaction can be used for the preparation of highly tritium-labeled (+)-MK-801 and 7-OH-DPAT with retention of their physiological activities.
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Abbreviations
- HS:
-
hydrogen spillover
- HSCIE:
-
high-temperature solid-phase catalytic isotope exchange
- 7-OH-DPAT:
-
R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetraline
- MK-801:
-
(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclopenten-5,1-imine
References
Zolotarev, Yu.A., Kozik, V.S., Zaitsev, D.A., Dorokhova, E.M., and Myasoedov, N.F., Dokl. Akad. Nauk SSSR, 1989, vol. 308, pp. 1146–1151.
Zolotarev, Yu.A., Laskatelev, E.V., Kozik, V.S., Dorokhova, E.M., Rozenberg, S.G., Borisov, Yu.A., and Myasoedov, N.F., Izv. Akad. Nauk, Ser. Khim., 1997, no. 4, pp. 757–762.
Zolotarev, Y.A., Borisov, Y.A., and Myasoedov, N.F., J. Phys. Chem. A, 1999, vol. 103, pp. 4861–4864.
Borisov, Yu.A. and Zolotarev, Yu.A., Zh. Fiz. Khim., 2002, vol. 76, pp. 727–731.
Kovalitskaya, Yu.A., Kolobov, A.A., Kampe-Nemm, E.A., Zolotarev, Yu.A., Yurovskii, V.V., Sadovnikov, V.B., Lipkin, V.M., and Navolotskaya, E.V., Bioorg. Khim., 2008, vol. 34, pp. 29–35 [Russ. J. Bioorg. Chem. (Engl. Transl.), vol. 34, pp. 24–29].
Kovalitskaya, Yu.A., Sadovnikov, V.B., Kolobov, A.A., Zolotarev, Yu.A., Yurovsky, V.V., Lipkin, V.M., and Navolotskaya, E.V., Bioorg. Khim., 2008, vol. 34, pp. 36–62 [Russ. J. Bioorg. Chem. (Engl. Transl.), vol. 34, pp. 30–36].
Zolotarev, Yu.A., Kozic, V.S., Zaitsev, D.A., Dorokhova, E.M., and Myasoedov, N.F., J. Radioanal. Nucl. Chem. Art., 1992, vol. 162, pp. 3–14.
Zolotarev, Yu.A., Dadayan, A.K., and Borisov, Yu.A., Bioorg. Khim., 2005, vol. 31, pp. 3–21 [Russ. J. Bioorg. Chem. (Engl. Transl.), vol. 31, pp. 1–17].
Lipton, S.A., Nature Neurosci., 2008, vol. 11, pp. 381–382.
Wong, E.H.F., Kemp, J.A., Priestley, T., Knight, A.R., Woodruff, G.N., and Iversen, L.L., Proc. Natl. Acad. Sci. USA, 1986, vol. 83, pp. 7104–7108.
Ricci, A., Collier, W.L., Rossodivita, I., and Amenta, F., J. Auton. Pharmacol., 1991, vol. 11, pp. 121–127.
Daly, S.A. and Waddington, J.L., Neuropharmacology, 1993, vol. 32, pp. 509–510.
Hillefors, M. and von Euler, G., Neurochem. Int., 2001, vol. 38, pp. 31–42.
Zolotarev, Yu.A., Dorokhova, E.M., Nezavibatko, V.N., Borisov, Yu.A., Rosenberg, S.G., Velikodvorskaia, G.A., Neumivakin, L.V., Zverlov, V.V., and Myasoedov, N.F., Amino Acids, 1995, vol. 8, pp. 353–365.
Franklin, P.H. and Murray, T.F., Mol. Pharmacol., 1992, vol. 41, pp. 134–146.
LePage, K.T., Ishmael, J.E., Low, C.M., Traynelis, S.F., and Murray, T.F., J. Neuropharmacol., 2005, vol. 49, pp. 1–16.
Fontana, A.C., Guizzo, R., Beledoni, R.O., Silva, A.R., Coimbra, N.C., and Amara, S.G., British. J. Pharm., 2003, vol. 139, pp. 275–280.
Hood, W.F., Gray, N.M., Dappen, M.S., Watson, G.B., Compton, R.P., and Cordi, A.A., J. Pharm. Exp. Ther., 1992, vol. 262, pp. 654–662.
Bresink, I., Danysz, W., Parsons, C.G., Tiedtke, P., and Mutschler, E., J. Neuron. Transm., 1995, vol. 10, pp. 11–26.
Reynolds, I.J., Murphy, S.N., and Miller, R.J., Proc. Natl. Acad. Sci. USA, 1987, vol. 84, pp. 7744–7748.
Wong, E.H., Knight, A.R., and Woodruff, G.N., J. Neurochem., 1988, vol. 50, pp. 274–281.
Levesque, D., Diaz, J., and Pilon, C., Proc. Natl. Acad. Sci. USA, 1992, vol. 89, pp. 8155–8159.
Wallace, D.R., Owens, J., and Booze, R.M., Live Sci., 1998, vol. 63, pp. 275–280.
Hillefors, M. and von Euler, G., Neurochem. Int., 2001, vol. 38, pp. 31–42.
Schwab, R.S., Poskanzer, D.C., England, A.C., and Young, R.R., Jama, 1972, vol. 222, pp. 792–795.
Val’dman, E.A., Voronina, T.A., and Nerobkova, L.N., Eksp. Klin. Farmakol., 1999, vol. 62, pp. 3–6.
Zolotarev, Y.A., Dadayan, A.K., Bocharov, E.V., Borisov, Y.A., Vaskovsky, B.V., Dorokhova, E.M., and Myasoedov, N.F., Amino Acids, 2003, vol. 24, pp. 325–333.
Lowry, O.H., Rosebrough, N.J., Farr, A.L., and Randell, R.J., J. Biol. Chem., 1951, vol. 193, pp. 265–275.
Chang, K.-J., Jacobs, S., and Cuatrecasas, P., Biochim. Biophys. Acta, 1975, vol. 406, pp. 294–303.
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Original Russian Text © Yu.A. Zolotarev, Yu.Yu. Firsova, A. Abaimov, A.K. Dadayan, V.S. Kosik, A. V. Novikov, N.V. Krasnov, B. V. Vaskovskii, I.V. Nazimov, G.I. Kovalev, N.F. Myasoedov, 2009, published in Bioorganicheskaya Khimiya, 2009, Vol. 35, No. 3, pp. 323–333.
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Zolotarev, Y.A., Firsova, Y.Y., Abaimov, A. et al. Ligands of glutamate and dopamine receptors evenly labeled with hydrogen isotopes. Russ J Bioorg Chem 35, 296–305 (2009). https://doi.org/10.1134/S1068162009030030
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DOI: https://doi.org/10.1134/S1068162009030030