Estrone sulfatase

The biologically inactive estrone sulfate (EIS) and dehydro-epiandrosterone-sulfate (DHEAS) are the most abundant circulating estrogenic precursors in the plasma of post-menopausal women [103]. Desulfation of inactive steroid-3-0-sulfates by estrone-sulfatase (STS) plays a key role in the regulation of levels of receptor-active estrogenic steroids (estradiol and androstenediol) in breast cancer cells (Fig. 9). There is strong evidence suggesting that estrone sulfatase (STS) and DHEA-sulfatase are the same enzyme [103]. 

Fig. 9 Enzymatic mechanism involved in the formation of estrogens. A The sulfatase pathway. B,C Structure of the potent STS inhibitors EMATE and COUMATE. D New pharmacophore for the inhibition of estrone sulfatase R general carbon backbone (aromatic or aliphatic), X electron withdrawing groups (e.g. nitro), Y additional functionality including fused or adjacent/remote ring structures so as to meet the log requirement...

Human estrone sulfatase is an enzyme that maintains elevated levels of estrogens within certain types of tumor cells. The enzyme is associated with a network of membranes within cells and relies on a pair of transmembrane helices that hold the enzyme to the surface of the membrane. The majority of the over 550-residue protein has a tertiary structure with a roughly spherical shape. A section of the chain loops away from the main structure. This loop contains two a-helices that twice cross a membrane and maintain the correct placement of the enzyme within the cell. a-Helices that hold a protein in place are called membrane anchors.2... 

W., Osawa, Y., Ghosh, D. Structure of Human Estrone Sulfatase Suggests Functional Roles of Membrane Association. J. Biol. Chem. 2003, 278, 22989-22997. 

Huang, Z., Fasco, M.J., and Kaminsky, L.S. 1997. Inhibition of estrone sulfatase in human liver microsomes by quercetin and other flavonoids. J. Steroid Biochem. Mol. Biol. 63, 9-15. 

Enzyme-catalysed desulfuration of steroids plays an important role in steroid biosynthesis and may provide a source of steroids in the growth and proliferation of breast cancer. Inhibition studies of estrone sulfatase with both steroidal and non-steroidal phosphate compounds have now shown that the best inhibitors contain phosphate mono anions and that the basic structure for inhibition does not require the steroid nucleus. ... 

Ahmed S, Owen CP, James K, Patel CK, Patel M. Acid dissociation constant, a potential physicochemical factor in the inhibition of the enzyme estrone sulfatase (ES). Bioorg Med Chem Lett 2001, 9 Apr ll(7) 899-902. 

The pK a and therefore the physicochemical properties of a series of aminosulfonate-based compounds of phenol is correlated with the irreversible inhibition of the enzyme estrone sulfatase (ES). A strong correlation exists between the observed pK a and inhibitory activity. The stability of the phenoxide ion, as indicated by the acid dissociation constant, is an important factor in the irreversible inhibition of this enzyme. 

Estrone 3-0-sulfamate [148672-09-7] M 349.5. Estrone 3-0-sulfamate is purified by silica gel flash chromatography to give a product with one spot on TLC. It is an active site-directed inhibitor of estrone sulfatase, i.e. a time-dependent enzyme inactivator. [Woo et al. J Med Chem 39 1349 7996, Purohit et al. Biochemistry 34 11508 1995.]... 

Iwamori, M., Moser, H. W., and Kishimoto, Y., Solubilization and partial purification of steroid sulfatase from rat liver Characterization of estrone sulfatase. Arch. Biochem. Biophys. 174, 199-208 (1976). 

Lakshmi, S., and Balasubramanian, A. S., Studies on the chaotropically solubilized arylsulfatase C and estrone sulfatase of sheep brain. Biochim. Biophys. Acta 567, 184-195 (1979). 

Mathew, J., and Bala subramanian, A. S., Arylsulfatase C and estrone sulfatase of sheep hypothalamus, preoptic area and mid brain Separation by hydrophobic interaction chromatography and evidence for diferences in their lipid environment. J. Neurochem. 39,1205-1209 (1982). 

Sulfamate A AIkylation. 7V,7V Dialkylation of TcesNHa occurs smoothly under biphasic conditions (Na0H-H20/CH2Cl2) using "Bu4NBr as a phase-transfer catalyst (eq 10). TcesNH2 and related sulfamate derivatives have been shown to act as inhibitors of estrone sulfatase. ... 

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