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Disorders of keratinization and other genodermatoses
Published in Rashmi Sarkar, Anupam Das, Sumit Sethi, Concise Dermatology, 2021
This is a relatively uncommon form of ichthyosis caused by the deficiency of the enzyme steroid sulfatase. Because of an X-linked recessive pattern of inheritance, a majority of the affected individuals are males. Females act as carriers of the mutation.
Multiple sulfatase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Deficiency of arylsulfatase A would be consistent with clinical features of MLD. The deficiency of steroid sulfatase is responsible for the skin lesions of X-linked ichthyosis. Among the enzymes of mucopolysaccharide metabolism: (1) deficiency of iduronate sulfatase provides manifestations of Hunter syndrome; (2) deficiency of heparan sulfatase yields the impaired mental development and cerebral features of Sanfilippo A disease; (3) deficiency of N-acetylglucosamine-6-sulfatase, those of Sanfilippo B disease; (4) deficiency of N-acetylgalactosamine-6-sulfatase gives rise to features of Morquio disease; and (5) deficiency of N-acetylgalactosamine-4-sulfatase, also known as arylsulfatase B, causes features of Maroteaux-Lamy disease, including corneal clouding. Obviously, different degrees of deficiency or amounts of residual enzyme activity would be expected to lead to quite different phenotypes. A number of different clinical phenotypes have been delineated [4], including the classic late infantile form, a neonatal form, a juvenile form, and a Saudi variant.
Disorders of keratinization and other genodermatoses
Published in Ronald Marks, Richard Motley, Common Skin Diseases, 2019
Histologically, there is a minor degree of epidermal thickening and mild hypergranulosis. Biochemically, affected male subjects show a steroid sulfatase deficiency, but for diagnostic purposes, fibroblast, lymphocyte or epidermal cell cultures are tested. The steroid sulfatase abnormality results in excess quantities of cholesterol sulfate in the stratum corneum with diminished free cholesterol. This has been used as the basis of a diagnostic test and has been suggested as the underlying biochemical basis for the abnormal scaling.
Steroid sulfatase inhibitors: the current landscape
Published in Expert Opinion on Therapeutic Patents, 2021
Hanan S. Anbar, Zahraa Isa, Jana J. Elounais, Mariam A. Jameel, Joudi H. Zib, Aya M. Samer, Aya F. Jawad, Mohammed I. El-Gamal
Steroid sulfatase enzyme is a monomer that has a molecular mass of 63 kDa that consists of an N-terminal signal peptide of 21–23 amino acids, four potential and two functional glycosylation sites such as Asn4, and Asn259[15]. The enzyme contains Ca2+ as a cofactor and ten catalytically important amino acid residues: Arg35, Arg36, Arg78, Arg342, Lys134, Lys368, His136, His290, Gln343, and N-formylglycine (FGly75)[16]. However, the three-dimensional structure of STS presents a globular polar domain with the catalytic site, and the putative transmembrane domain that contains two antiparallel hydrophobic alpha helices [17]. Previous researches viewed that STS has been located in the membranes of the endoplasmic reticulum and humane placenta[18]. Interestingly, STS expression was found to be significantly increased in placenta than other tissues [19,20]. It has been found also in mammary gland, skin, liver, lung, ovary, adrenal gland, endometrium, brain, and in the intestine [19,21,22]. Moreover, STS has been found in prostatic tissue, precisely in prostatic epithelium where the highest STS activity was detected [23,24]. Furthermore, STS activity is stronger in fetal tissues. STS expression is higher in fetal comparing to adult tissues, especially in the brain and the intestine [19].
Transition metal-catalysed A-ring C–H activations and C(sp2)–C(sp2) couplings in the 13α-oestrone series and in vitro evaluation of antiproliferative properties
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Péter Traj, Ali Hazhmat Abdolkhaliq, Anett Németh, Sámuel Trisztán Dajcs, Ferenc Tömösi, Tea Lanisnik-Rizner, István Zupkó, Erzsébet Mernyák
Concerning the modification of the phenolic hydroxy function of oestrone derivatives, important structure–activity relationships are described in the literature. Introduction of a sulfamoyl moiety onto 3-OH of oestrogens resulted in compounds possessing remarkable biological activities56–59. Their aryl O-sulfamate pharmacophore facilitated steroid sulfatase inhibitory activity, leading to anticancer effect. Nevertheless, certain oestrone sulfamates proved to be active against triple-negative breast cancer owing to their triple effect60. Beside their microtubule disruptor properties, they displayed proapoptotic and anti-angiogenic action60. Furthermore, carbamoylation of oestrogens at C-3-O afforded N-mustard carbamates as potent cytotoxic agents against prostatic adenocarcinoma61.
Synthesis of substituted 15β-alkoxy estrone derivatives and their cofactor-dependent inhibitory effect on 17β-HSD1
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Bianka Edina Herman, Anita Kiss, János Wölfling, Erzsébet Mernyák, Mihály Szécsi, Gyula Schneider
It was shown that neither the presence of the phenolic hydroxyl group nor the hydrogen bonding of the C3 function is essential to the effective 17β-HSD1 binding of estrone derivatives17. This tolerance provides further options for the modulation of enzyme inhibition and other biological effects of the candidate compounds. Accordingly, several 3-methoxy analogues were tested as 17β-HSD1 inhibitors12,13 presumably that they exert reduced estrogenicity compared to estrone possessing phenolic hydroxy group18. Estrone 3-sulfamate analogues in this series tend to show moderate 17β-HSD1 inhibition13. However, the sulfamate moiety may lead to an inhibitory effect against steroid sulfatase (STS), another enzyme playing a central role in 17β-estradiol biosynthesis. Such a dual inhibitory effect was recently proposed to be beneficial as it should result in a stronger suppression of estrogen biosynthesis compared to selective inhibition of 17β-HSD119. Steroidal sulfamates may be delivered to the tumour by the carbonic anhydrase II, and evolve targeted actions20.