Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most freque...

https://www.nejm.org/doi/pdf/10.1056/NEJMra021561

Congenital adrenal hyperplasia

Aryl sulfonyl chlorides (e.g. Ts-Cl) are beloved of organic chemists as the most commonly used S(VI) electrophiles, and the parent sulfuryl chloride, O2 S(VI) Cl2 , has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the S(VI) Cl bond is exceedingly sensitive to reductive collapse yielding S(IV) species and Cl(-) . Fortunately, the use of sulfur(VI) fluorides (e.g., R-SO2 -F and SO2 F2 ) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid-20th century. Here we seek to revive it, along with John Hyatt's unnoticed 1979 full paper exposition on CH2 CH-SO2 -F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2 F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of SF bonds for SO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed.

Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17β–hydroxysteroid dehydrogenase (17β–HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17β–HSD type 3 isozyme that shares 23% sequence identity with other 1 7β–HSD enzymes, uses NADPH as a cofactor, and is expressed predominantly in the testes. The 17βHSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17βHSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17β–HSD type 3 isozyme.

Male pseudohermaphroditism caused by mutations of testicular 17β-hydroxysteroid dehydrogenase 3

Steroid hormones, which are synthesized in the adrenal gland, gonads and placenta, exert a large array of biological effects on the nervous system. In particular, steroid hormones play an important role in the development, growth, maturation, and differentiation of the central nervous system (CNS)2

Neurosteroids: Expression of Steroidogenic Enzymes and Regulation of Steroid Biosynthesis in the Central Nervous System

Sulfonyl fluoride electrophiles have found significant utility as reactive probes in chemical biology and molecular pharmacology. As warheads they possess the right balance of biocompatibility (including aqueous stability) and protein reactivity. Their functionality is privileged in this regard as they are known to modify not only reactive serines (resulting in their common use as protease inhibitors), but also context-specific threonine, lysine, tyrosine, cysteine and histidine residues. This review describes the application of sulfonyl fluoride probes across various areas of research and explores new approaches that could further enhance the chemical biology toolkit. We believe that sulfonyl fluoride probes will find greater utility in areas such as covalent enzyme inhibition, target identification and validation, and the mapping of enzyme binding sites, substrates and protein–protein interactions.

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Sulfonyl fluorides as privileged warheads in chemical biology

The influence of various factors upon testicular enzymes related to steroidogenesis.

Purification and characterization of rat adrenal 3β-hydroxysteroid dehydrogenase with steroid 5-ene-4-ene-isomerase

Testicular and adrenal 3β-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase

Studies on enzyme reactions related to steroid biosynthesis: II. submicrosomal distribution of the enzymes related to androgen production from pregnenolone and of the cytochrome P-450 in testicular gland of rat

Inano Hiroshi

Papers

The influence of various factors upon testicular enzymes related to steroidogenesis.

Purification and characterization of rat adrenal 3β-hydroxysteroid dehydrogenase with steroid 5-ene-4-ene-isomerase

Testicular and adrenal 3β-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase

Studies on enzyme reactions related to steroid biosynthesis: II. submicrosomal distribution of the enzymes related to androgen production from pregnenolone and of the cytochrome P-450 in testicular gland of rat

Studies on the enzymes [related to steroidogenesis in [testicular tissue of guinea pig