Steroid, acids conjugates

Miller-Larsson A, Mattsson H, Hjertberg E, Dahlback M, Tunek A, Brattsand R (1998) Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 26(7) 623-630. 

Polymastiamide A (579), an antimicrobial steroid with an unusual side chain modification involving an amide bond to a non-protein amino acid, was isolated from the Norwegian marine sponge Polymastia boletiformis. The structure of polymastiamide A (579) was elucidated by analysis of spectroscopic data and chemical interconversions [470]. Polymastiamides B-F (580-584), additional amino acid conjugates of steroids, were later isolated from the same sponge [471],... 

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, Borst P. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J 2003 371 361-367. 

Using steroid as supporting scaffold, the reaction of diamine 67, diisocyanide 68 (both being derived from lithocholic acid), acetic acid and formaldehyde afforded the macrocycle 69a in 58% yield as a mixture of head-to-tail and head-to head cyclic dimers ((1), Scheme 20 for the sake of clarity, only the head-to-tail regioi-somer was shown) [96-98]. On the other hand, the reaction of diacid 70, diisocyanide 68, isopropylamine and formaldehyde afforded the steroid-peptoid conjugate... 

In 1956 our laboratory, in collaboration with Beiser and Lieberman, became interested in preparing steroid-protein conjugates that were to be used to elicit antisteroid antibodies. An examination of the literature at that time showed that the azo coupling techniques of Landsteiner were still dominant. Like him, we chose to use the serum albumins because they were inexpensive and likely to yield soluble conjugates. However, an examination of the amino acid content of bovine serum albumin (BSA) (Fig. 1) convinced us that substitution by such relatively complex haptens as steriods should be attempted by reaction with the more plentiful c-amino groups of the lysine residues rather than by an azo coupling reaction with tyrosine, tryptophan, and imidazole residues. This meant forma-... 

A procedure introduced by us for steroid-protein conjugates was the estimation of the remaining free amino groups with the dinitrophenylation technique of Sanger. e-Dinitrophenyllysine was not isolated but was estimated directly by spectrophotometry after ether extraction of the acid hydrolyzate. A control with unsubstituted carrier was always run concomitantly, and the difference between the two was taken to be the extent of substitution by hapten. 

OatplaS was cloned fromratretinaandintestine [41,44]. Consequently, theexpression of OatplaS protein could not be demonstrated unequivocally in liver or kidney. In addition, OatplaS rather than Oatplal is expressed at the apical plasma membrane of rat choroid plexus epithelial cells [45]. As Oatplal is not expressed in the intestine, expression of OatplaS could clearly be shown at the apical membranes of small intestinal epithelial cells [44]. The 670-amino acid protein shares 80% amino acid identity with Oatplal. OatplaS can transport bile salts, steroid hormone conjugates, thyroid hormones, cardiac glycosides, and oligopeptides (Table 3.2) [26, 46, 47]. 

Roda, A., Roda, E., Festi, D., Aldini, R., Mazella, C., Sama, C., and Barbara, L., A radioimmunoassay for lithocholic acid conjugates in human serum and liver tissue. Steroids 32, 13-24 (1978). 

In the first place the discovery of the secretion of DHA-sulfate by the adrenal cortex in apparently major quantities suggested a hitherto completely unsuspected role of steroid sulfates in steroid biosynthesis and metabolism. Second, a number of steroid metabolites conjugated with two molecules of glucuronic or sulfuric acid were discovered, particularly in pregnancy urine, amniotic fluid, and in perfused placentofetal preparations. Finally, isotopic studies revealed several cases in which administered doubly labeled steroid conjugates were metabolized in the steroid part of the molecule without hydrolysis of the conjugate (e.g., D4, R5 cf. B5). 

Phenolic compounds, as well as some steroid hormones and the dicar-boxylic amino acids (PIO), are found in urine as glucuronic acid conjugates. 

Bile salts with a steroid structure appear to be confined to vertebrates (76). In some evolutionarily more primitive vertebrates, the major bile salts are sulfate esters of polyhydroxy C27- and C26-steroids and/or taurine-conjugated C27-steroid acids. In other primitive vertebrates, C24 bile acids, usually cholic acid and/or allocholic acid, or mixtures of primitive bile salts (bile alcohols and C27 bile acids) and modern bile salts (C24 bile acids) occur. Most of the work concerning the structure and occurrence of primitive bile salts has been carried out in the laboratories of G. A. D. Haslewood and T. Kazuno, and Haslewood and collaborators have accumu-... 

Besides influencing the critical micellar temperature, the number and position of hydroxy groups also influence the critical micellar concentration. The critical micellar concentration of dihydroxy bile acids is significantly below that of trihydroxy acids (1,63), but no values have been reported for monohydroxy acids. Conjugation with glycine or taurine does not appear to have any particular effect on those properties of bile acids which are related to the steroid nucleus, provided that experiments are carried out at pH sufficiently alkaline that all bile acid molecules present are ionized (64). 

Besides hormonal steroid conjugates (Figure 2.7), bile alcohol and bile acid conjugates can also be analyzed by shotgun steroidomics. These metabolites are often elevated in abundance in plasma as a consequence of an inborn error of bile acid biosynthesis or as a consequence... 

Steroid hormones can be inactivated by conjugation and degradation. Conjugation involves the formation of either glucuronides or aryl sulfates. Steroids are conjugated with glucuronic acid in the presence of a liver microsomal enzyme and UDP-glucuronic acid. 

After deproteinization of bile, Turnberg and Anthony-Mote (94) were able to quantitate bile acids directly with a NAD-dependent steroid oxido-reductase from a Pseudomonas strain. The suitable concentration range was 10-80 mg of bile acids per 100 ml. The amounts of individual bile acids could be determined after preparative thin-layer chromatography, either before or after hydrolysis of bile acid conjugates. 

Chemically, the bile acids are hydroxylated derivatives of cholanic acid, a tetracyclic steroid acid of 24 carbon atoms. The acids occur in nature largely as the water-soluble sodium salts of peptide conjugates of glycine and taurine. The free acids are liberated by saponification or specific enzyme hydrolysis. The chemistry of the bile acids has been reviewed in Chapter 1 of this volume (1). In view of their highly polar nature, special attention is called to the recent discovery of the cholic acid conjugates of ornithine (2, 3) and the 3a-sulfate esters of glycolithocholic and taurolithocholic acids (4). 

---