An inhibitor of S-adenosylhomocysteine
3-Deazaadenosine (3-DZA) is an inhibitor of S-adenosylhomocysteine hydrolase (Ki = 3.9 μM).1,2 It has anti-inflammatory properties, inhibiting leukocyte adhesion and chemotaxis, lymphocyte-mediated cytolysis, phagocytosis, degranulation, and NF-κB signaling.3,4 3-DZA also has antiviral and antibacterial activities.1,5,6
1.Chiang, P.K.Biological effects of inhibitors of S-adenosylhomocysteine hydrolasePharmacol. Ther.77(2)115-134(1998) 2.Gordon, R.K., Ginalski, K., Rudnicki, W.R., et al.Anti-HIV-1 activity of 3-deaza-adenosine analogs: Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congenersEur. J. Biochem.270(17)3507-3517(2003) 3.Jurgensen, C.H., Huber, B.E., Zimmerman, T.P., et al.3-Deazaadenosine inhibits leukocyte adhesion and ICAM1 biosynthesis in tumor necrosis factor-stimulated human endothelial cellsJ. Immunol.144(2)653-661(1990) 4.Jeong, S.Y., Ahn, S.G., Lee, J.H., et al.3-Deazaadenosine, a S-adenosylhomocysteine hydrolase inhibitor, has dual effects on NF-κB regulationJ. Biol. Chem.274(27)18981-18988(1999) 5.Long, M.C., Allan, P.W., Luo, M.Z., et al.Evaluation of 3-deaza-adenosine analogues as ligands for adenosine kinase and inhibitors of Mycobacterium tuberculosis growthJ. Antimicrob. Chemother.59(1)118-121(2007) 6.Huggins, J., Zhang, Z.X., and Bray, M.Antiretroviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit ebola virus in vitro and in a lethal mouse modelJ. Infect. Dis.179(Suppl. 1)S240-S247(1999)
Cell experiment: | The HIV-1 strains A012 and A018 are used in the assay. Inhibition of p24 antigen is measured. Briefly, PHA-stimulated peripheral blood mononuclear (PBMCs) are incubated with either HIV-1 strain for 1 h at 37°C at 200-fold the 50% tissue culture infectious dose (TCID50) of the virus stock per 2 × 105 PBMC cells. The TCID50 is defined as the amount of virus stock at which 50% of the inoculated wells are positive. Cells are then grown in microtiter plates with different drug concentrations at 2 × 105 cells per well. On day 4, cells are resuspended and split 1:3 with fresh media and 3-Deazaadenosine. Supernatant p24 antigen is determined on day 7 by ELISA[1]. |
参考文献: [1]. Gordon RK, et al. Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners. Eur J Biochem. 2003 Sep;270(17):3507-17. | |
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