Differentiation inhibition

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

Dhindsa, R.S. Cleland, R.E. (1975). Water stress and protein synthesis. I. Differential inhibition of protein synthesis. Plant Physiology, 55, 778-81. 

Electrophoretic methods of separation of LD Tsoenzymes have become routine in clinical laboratories. Efforts are now being made to standardize the methodologies used for LD isoenzymes, particularly by Rosalki (38). The preferred methods are based on electrophoresis on a solid medium, so that the several bands may be scanned instrumentally. Differential isoenzyme inhibition with urea or other inhibitors is based on the fact that the heart LD isoenzyme is more resistant to inhibition than other isoenzymes. However, the analyst then has the problem of allocating the observed degree of inhibition between the different isoenzymes of a given sample, a problem that has not been resolved satisfactorily thus far. Hence, differential inhibition is not as reliable for isoenzyme separation as is electrophoresis. 

Alkaline phosphatase assays based on 3-glycerophosphate now appears to be obsolete, and methods buffered by either glycine or barbital are also obsolete as these buffers inhibit ALP or are poor buffers. Serum alkaline phosphatase is known to be composed of several isoenzymes which presumably arise from bone, liver, intestine, and placenta. The placental alkaline phosphatase is known to be much more resistant to heat denaturation than the other isoenzymes, and this resistance provides a simple test for it (5). The other enzymes can be separated through the differential inhibition by phenylalanine, by electrophoresis and by specific antibodies. However, the clinical usefulness of the results obtained is in doubt (23). 

NAKANE H (1991) Differential inhibition of HIV-reverse transcriptase and various DNA polymerases by theaflavins , in Proc of Intern Symp on Tea Sci, 26-29 August, 1991, Shizuoka, Japan, 282-6. 

Grudzien, E., Kalek, M., Jemielity, J., Darzynkiewicz, E., and Rhoads, R. E. (2006). Differential inhibition of mRNA degradation pathways by novel cap analogs. J. Biol. Chem. 281, 1857-1867. 

S. Andre, B. Liu, H.-J. Gabius, and R. Roy, First demonstration of differential inhibition of lectin binding by synthetic tri- and tetravalent glycoclusters from cross-coupling of rigidified 2-propynyl lactoside, Org. Biomol. Chem., 1 (2001) 3909-3916. 

Cho SY, Kim JH, Paik YK (1998) Cholesterol biosynthesis from lanosterol differential inhibition of sterol delta 8-isomerase and other lanosterol-converting enzymes by tamoxifen. Mol Cells 8(2) 233-239... 

Vandenberg, R. J., Mitrovic, A. D., and Johnston, G. A. (1998) Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions. Mol. Pharmacol. 54,189-196. 

Fridovich, I., Handler, P., Xanthine oxidase. V. Differential inhibition of the reduction of various electron acceptors. J. Biol. Chem. 237 (1962), p.916-921... 

The ability of different drugs to differentially inhibit and/or induce individual cytochrome P-450 isoenzymes has become critical in assessing the potential safety of drug molecules. Table 18.7 presents an overview of some of what we have come... 

Wiebel, F. J., Leutz, J. C., Diamond, L., and Gelboin, H. V. Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in microsomes from rat tissues differential inhibition and stimulation by benzoflavones and orqanic solvents. Arch. Biochem. Biophys. (1971) 144 78-86. 

Teng L, Crooks PA, Sonsalla PK, Dwoskin LP. (1997). Lobeline and nicotine evoke [3H]overflow from rat striatal slices preloaded with [3H]dopamine differential inhibition of synaptosomal and vesicular [3H]dopamine uptake. J Pharmacol Exp Ther. 280(3) 1432-44. 

Richon VM, Emihani S, Verdin E, Webb Y, Breslow R, Rifkind RA, Marks PA (1998) A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad... 

Pekthong D, Martin H, Abadie C, Bonet A, Heyd B, Mantion G, richert L. (2008) Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J Ethonopharmacol 115 432-440. 

The family of HDAC enzymes has been named after their first substrate identified, i.e., the nuclear histone proteins. Histone proteins (H2A, H2B, H3 and H4) form an octamer complex, around which the DNA helix is wrapped in order to establish a condensed chromatin structure. The acetylation status of histones is in a dynamic equilibrium governed by histone acetyl transferases (HATs), which acetylate and HDACs which are responsible for the deacetylation of histone tails (Fig. 1). Inhibition of the HDAC enzyme promotes the acetylation of nucleosome histone tails, favoring a more transcriptionally competent chromatin structure, which in turn leads to altered expression of genes involved in cellular processes such as cell prohferation, apoptosis and differentiation. Inhibition of HDAC activity results in the activation of only a limited set of pre-programmed genes microarray experiments have shown that 2% of all genes are activated by structmally different HDAC inhibitors [1-5]. In recent years, a growing number of additional nonhistone HDAC substrates have been identified, which will be discussed in more detail below. 

Seynaeve CM, Kazanietz MG, Blumberg PM, et al. Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Mol Pharmacol 1994 45 1207-1214. 

Leslie, E.M. et al. (2007) Differential inhibition of rat and human Na + -dependent taurocholate cotransporting polypeptide (NTCP/SLCIOAI) by bosentan a mechanism for species differences in hepatotoxicity. Journal of Pharmacology and Experimental Therapeutics, 321 (3), 1170-1178. 

The most extensive formal validation study in this area addressed whole embryo culmre (WEC), micromass (MM), and the embryonic stem cell test (EST) (26). This validation study proved a great learning experience in view of understanding the value of a study with a limited amount of diverse compounds in terms of extrapolation to the universe of chemicals. Subsequent application of the validated EST taught us that the 80% predictability was not reproduced with additional compounds (27). One of the issues underlying this discrepancy was in the mathematical prediction model used, which did not always appear to match the biology of the assay in terms of observed differentiation inhibition. 

ZO203 Ono, K., H. Nakane, M. Fukushima, J. C. Chernmann, and F. Barre-Sinoussi. Differential inhibition of the activities of reverse transcriptase and various cellar DNA polymerases by a traditional Kampo drug, Sho-Saiko-To. Biomed Pharmacother 1990 44 13-16. 

Although the mechanism of action of IFN-a against HCL is incompletely understood, it most likely relates to IFN-a-induced B-cell differentiation, inhibition of hairy-cell responsiveness to B-cell growth factors, or activation of antineoplastic immune cell function [83]. 

Morgan, R. O., and Newby, A. C. (1989). Nitroprusside differentially inhibits ADP-stimulated calcium influx and mobilization in human platelets. Biochem. J. 258, 447-454. 

Famet CM, Wang B, Lipford JR, Bushman FD. Differential inhibition of HIV-1 preintegration complexes and purified integrase protein by small molecules. Proc Natl Acad Sci USA 1996 93 9742-9747. 

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