Nucleotide phosphodiesterase

Beyond pharmaceutical screening activity developed on aminothiazoles derivatives, some studies at the molecular level were performed. Thus 2-aminothiazole was shown to inhibit thiamine biosynthesis (941). Nrridazole (419) affects iron metabohsm (850). The dehydrase for 5-aminolevulinic acid of mouse liver is inhibited by 2-amino-4-(iS-hydroxy-ethyl)thiazole (420) (942) (Scheme 239). l-Phenyl-3-(2-thiazolyl)thiourea (421) is a dopamine fS-hydroxylase inhibitor (943). Compound 422 inhibits the enzyme activity of 3, 5 -nucleotide phosphodiesterase (944). The oxalate salt of 423, an analog of levamisole 424 (945) (Scheme 240),... 

Inhibition of the enzyme activity of 3, 5 -nucleotide phosphodiesterase 69GEP1809013... 

Cheung, W. Y. (1970). Cyclic 3, 5 -nucleotide phosphodiesterase Demonstration of an activator. Biochem. Biophys. Res. Commun. 38, 533-538. 

Butcher, R.W., and Sutherland, E.W. (1962) Adenosine 3, 5 -phosphate in biological materials. I. Purification and properties of cyclic 3, 5 -nucleotide phosphodiesterase... 

Marani E, Boekee A (1973) Aspects histo-enzymologiques de la localisation de I adenylcyclase, de la c.3, 5 -nucleotide phosphodiesterase, de la 5 -nueleotidase et de I alpha-glucanphosphorylase dans le cervelet de la souris. Bui /lisoc. des Anat. 57, 5555-5564. 

Farnham, C.J.M. 1975. Cytochemical localization of adenylate cyclase and 3, 5 -nucleotide phosphodiesterase in Dictyostelium. Exp. Cell Res. 91 36-46. 

There are 11 different PDE families (PDEl-11) with different substrate specificity, affinity, sensitivity to inhibitors, and tissue localization. In addition, there are exonucleases such as 5 -nucleotide phosphodiesterase (PDE 1) and 3 -nucleotide phosphodiesterase (PDE 11) that hydrolyze phosphodi-ester bounds. These enzymes have several known functions in nucleic acids. By using all these enzymes in a sensor surface and by measuring changes in fluorescence polarization it was concluded that YTX binds to cyclic nucleotide PDEl, with a calcium-dependent effect, PDE3, and PDE4, and shows high affinity by exonuclease PDE 1 [15,16]. 

Bryant FR, Benkovic SJ (1979) Stereochemical course of the reaction catalyzed by 5 -nucleotide phosphodiesterase from snake venom. Biochemistry 18 2825-2829... 

It seems likely that the metabolic effects of several hormones are mediated by adenosine 3, 5 -phosphate (cyclic AMP). The biochemical effects of this nucleotide have been discussed. 3-92 Cyclic AMP is synthesized from ATP by a reaction catalyzed by adenyl cyclase and it is rapidly inactivated by a cyclic 3, 5 -nucleotide phosphodiesterase which converts it to 5 -AMP.91 Cyclic AMP levels are Influenced by numerous hormones, (catecholamines, glucagon, ACTH, Insulin, and others).91 Most of these stimulate adenyl cyclase and Increase cyclic AMP levels, however, insulin... 

Uzunov, P., Revuelta, A., and Costa, E., 1975, Role for the endogenous activator 3, 5 -nucleotide phosphodiesterase in rat adrenal medulla. Mol. Pharmacol. 11 506. 

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