Retinoids chemical analysis

The ligand binding pocket of USP is filled by a fortuitous phospholipid co-purified and co-crystallized with the USP LBD that was fiirther characterized by mass-spectroscopic and chemical analysis [57]. In a similar way, recent crystallographic investigations of the retinoid-acid related orphan receptor (3 (ROR (3) [58] and of the heterodimeric complex RARa/RXRa [30] revealed an E.coli endogeneous fatty acid in the ROR (3 and in the RXRa subunit, respectively. 

Extraction, Separation, and Chemical Analysis of Retinoids Charles A. Frolik and James A. Olson... 

Rhodopsin is a seven ot-helix trans-membrane protein and visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In this photoreceptor, retinal is the chromophore bound by opsin protein, covalently linked to Lys296 by a Schiff base linkage. Kpega et al.64 have studied NMR spectra of Schiff bases being derivatives of all-frans retinal and amino-p-cyclodextrins as a model of rhodopsin, where p-cyclodextrin plays a role of a binding pocket. On the basis of analysis of the chemical shift differences for the model compound in the presence and in the absence of adamantane carboxylate, it has been shown that the derivative of 3-amino-p-cyclodextrin forms dimer in water and retinoid is inserted into p-cyclodextrin cavity [31]. 

One of the most important phenomena for analysis of the mechanism of action of retinoids in prevention of cancer is their ability to suppress the transformation of nonneoplastic C3H/10T1/2 mouse fibroblasts that have been exposed to the chemical carcinogen 3-methylcholanthrene. This was first reported by Merriman and Bertram (1979) using retinyl acetate, retinol, and retinaldehyde as the retinoids. Similar findings were reported by Harisiadis et al. (1978), who showed that motretinid (F3) could suppress radiation-induced transformation of the same cell line. A series of retinoids has been tested by Bertram (1980 see also Bertram et al., 1982) for their ability to suppress methylcholanthrene-induced transformation effects were evaluated over a test range from approximately 10 to 10 M. Retinyl acetate, A -(4-hydroxyphenyl) retinamide (E16), and retinylidene di-medone (C6) were found to be most effective, and A -benzoylretinylamine (B2) was only slightly effective. Surprisingly, all-rran -retinoic acid and 13-cw-reti-noic acid were ineffective in these tests the reason for these results is not clear. 

Retinyl acetate is sometimes used as internal standard for retinol analysis it is not ideal because it is an ester, not a free alcohol (and is hydrolyzed by saponification processes), but superior in principle to the use of tocol or other nonretinoid forms for retinoid quantitation. Substituted retinal oximes have been used as internal standards (93). 15-Methylretinol (94) is conceptually an excellent internal standard for retinol analysis, because of its very similar chemical structure and properties. 

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