- Human cellular retinaldehyde-binding protein has secondary thermal 9-cis-retinal isomerase activity
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Cellular retinaldehyde-binding protein (CRALBP) chaperones 11-cis-retinal to convert opsin receptor molecules into photosensitive retinoid pigments of the eye. We report a thermal secondary isomerase activity of CRALBP when bound to 9-cis-retinal. UV/vis and 1H NMR spectroscopy were used to characterize the product as 9,13-dicis-retinal. The X-ray structure of the CRALBP mutant R234W:9-cis-retinal complex at 1.9 A resolution revealed a niche in the binding pocket for 9-cis-aldehyde different from that reported for 11-cis-retinal. Combined computational, kinetic, and structural data lead us to propose an isomerization mechanism catalyzed by a network of buried waters. Our findings highlight a specific role of water molecules in both CRALBP-assisted specificity toward 9-cis-retinal and its thermal isomerase activity yielding 9,13-dicis-retinal. Kinetic data from two point mutants of CRALBP support an essential role of Glu202 as the initial proton donor in this isomerization reaction.
- Bolze, Christin S.,Helbling, Rachel E.,Owen, Robin L.,Pearson, Arwen R.,Pompidor, Guillaume,Dworkowski, Florian,Fuchs, Martin R.,Furrer, Julien,Golczak, Marcin,Palczewski, Krzysztof,Cascella, Michele,Stocker, Achim
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- PHOTOISOMERIZATION OF THE C18 KETONE IN THE VITAMIN A SERIES. SOLVENT EFFECT ON PHOTOISOMERIZATION OF COMPOUNDS RELATED TO RETINAL
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The directions of photoisomerization of polyenals and polyenones are believed to be controlled by the relative ordering of n,?* and ?,?* states.
- Ramamurthy, V.,Denny, M.,Liu, R. S. H.
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- Vinyltin acetals in terpenic and nor-terpenic synthesis
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Vinyltin acetals obtained by stannylmetallation of homopropargyl acetals with Bu3SnMgMe/CuCN (E configuration) or by titanation of the corresponding alkyltin acetals (Z configuration) have been proved to be efficient storable precursors for the stereoselective synthesis of terpenoids, under mild experimental conditions.Due to the presence of a nucleophilic centre (Csp2-Sn bond) and of a protected electrophilic centre, they are also useful intermediates for an iterative synthesis of retinal and nor-retinoids. - Keywords: vinyltin; acetal; vinyllithium; monoterpenoid; retinal; nor-retinoid
- Launay, Valerie,Beaudet, Isabelle,Quintard, Jean-Paul
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p. 937 - 946
(2007/10/03)
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- Palladium-catalysed vinylation of tertiary allylic alcohols: A new protocol for the synthesis of isoprenoid aldehydes.
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Heck vinylation of tertiary allylic alcohols with iodo-acetal Ic, followed by an acid catalysed acetal hydrolysis-dehydration reaction, furnished isoprenoid aldehydes regioselectively in high yields.
- Bienayme,Yezeguelian
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p. 3389 - 3396
(2007/10/02)
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- Retinal, derivatives and their therapeutic use
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Therapeutic as well as preventive measures to improve cosmetic conditions and to alleviate the symptoms of dermatologic disorders with retinal and its derivatives is disclosed. Cosmetic conditions and dermatologic disorders in humans and domestic animals in which retinal and its derivatives may be useful include age spots, wrinkles, warts, eczema, seborrheic keratoses, acne, oily skin, psoriasis, dandruff, xerosis, inflammatory and pruritic skin, disturbed keratinization skin changes associated with aging and possibly viral infections. Retinal and its derivatives include their stereoisomers, for example, all-trans, 13-cis, 11-cis, 9-cis, 7-cis, 11,13-cis and 9,13-cis vitamin A aldehydes, their hydrate, hemiacetal and acetal forms, and their adduct compounds. Compositions containing retinal or its derivative may be administered systemically such as orally, or topically to the affected areas of the skin.
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- A new prenylation method using the lithium enolate of prenal. Reaction with polyunsaturated aldehydes. A short access to retinal
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The enolate of prenal 1 prepared from the corresponding silyl enol ether 2 or enol acetate 3 led to a γ-regiospecific reaction with polyunsaturated aldehydes 4 yielding dihydropyrans 5 leading after hydrolysis to polyenals 7. This process allows the introduction of the isoprenyl skeleton. A synthesis of retinal, from β-ionylidenacetaldehyde is reported.
- Duhamel, Lucette,Guillemont, Jerome,Poirier, Jean-Marie,Chabardes, Pierre
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p. 4499 - 4500
(2007/10/02)
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- Photoisomerization of Hindered Poly-cis Isomers of Retinal. Regioselectivity And One -Photon-Multiple-Bond Isomerization.
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Direct irradiation of five dicis (7,9, 7,11, 7,13, 9,11 and 9,13) and one tricis (7,9,11) isomers of retinal led to regioselective isomerization at the 13,14 bond as well as multiple-bond isomerization.
- Ganapathy, Srinivasan,Liu, Robert S. H.
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p. 6957 - 6960
(2007/10/02)
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- Sensitized photoisomerization of all-trans- and 11-cis-retinal
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The photoisomerization of all-trans-retinal (all-trans) and 11-cis-retinal (11-cis) sensitized by a range of sensitizers (porphyrins, Zn-porphyrins, naphthacene and a Zn-phthalocyanine) with varying triplet energies above and below the vertical triplet energy of all-trans-retinal (E(T) = 149 kJ/mol) has been investigated by continuous illumination and HPLC analysis of the products. The composition of the photostationary states, the relative isomerization quantum yields of all-trans and 11-cis, and the primary product ratios are reported. One photon-one bond isomerizations are dominant. With Zn-TPP as sensitizer it is shown that 11-cis and possibly all-trans undergoes one photon-two bond isomerizations as well. The quantum yields of photoisomerization of 11-cis sensitized by biphenyl (E(T) = 275 kJ/mol) and anthracene (E(T) = 178 kJ/mol) were found to be identical. Absolute measurements allowed evaluation of the overall triplet isomerization quantum yield of 11-cis, Φ(iso)(T)(11-cis→) = 1.0 ± 0.2, from which the corresponding quantity for all-trans, Φ(iso)(T)(trans-→) = 0.15 ± 0.05, was obtained. The overall photoisomerization quantum yield of 11-cis with direct excitation at 254 nm was determined as Φ(iso)(d)(11-cis→) = 0.42 ± 0.05 assuming all-trans and 13-cis to be the primary products. Quenching rate constants of several of the sensitizer triplet states by retinal were measured by laser flash photolysis. Possible mechanisms that could account for the experimental results are discussed, and it is concluded that the photoisomerizations most likely involve the retinal triplet states as intermediates. Within this model the observed sensitizer triplet energy dependence of the primary product ratios suggests that the triplet states of the different retinal isomers are different mixtures of triplet excited species, and that the composition of these mixtures depends on the starting isomers as well as on the sensitizer triplet energy for energies below the vertical triplet energy of all-trans-retinal. In the light of a review of the existing literature on the direct and the sensitized photoisomerization of retinals these conclusions suggest substantial corrections to the accepted picture of retinal photochemistry.
- Jensen,Wilbrandt,Bensasson
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p. 7877 - 7888
(2007/10/02)
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- Thermal Sigmatropic Rearrangements of Vinylallenes Leading to 11-cis-Retinoids and the Novel Properties of 9-cis,11-cis,13-cis-Retinal and 11-cis,13-cis-Retinal
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The thermally induced sigmatropic hydrogen shift of vinylallene 5 provided a route to highly hindered 11-cis-retinoids.The coupling ot the hetero cuprate 14 with the propargyl benzoate 13b gave the vinylallene 5, which upon heating (69 deg C, 2 h) gave three geometrically isomeric retinoids: 11-sis (8), 11-cis,13-cis (9), and 9-cis,11-cis,13-cis (11).The fourth possible geometric isomer, 9-cis,11-cis (10), was unstable to the conditions of thermolysis and underwent further electrocyclizations to the tricyclic compound 22.The thermal rearramgement of 9,10-allene 5, though highly specific for the formation of 11-cis-retinoids, exhibits no selectivity in the formation of Δ9 and Δ13 double bonds.The highly hindered 11-cis,13-cis- and 9-cis,11-cis,13-cis-retinals, 9b and 11b, exhibit extraordinary electronic absorption spectra in that they exhibit their main maxima (302 nm) actually to the blue of the corresponding alcohols.The retinals 9b and 11b were thermally unstable and underwent clean isomerization to 13-cis-retinal and 9-cis,13-cis-retinal, respectively.
- Knudsen, Christopher G.,Chandraratna, Roshantha A. S.,Walkeapaeae, Leslie P.,Chauhan, Yeshpal S.,Carey, Stephen C.,et al.
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p. 1626 - 1631
(2007/10/02)
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- Studies on the Catalyzed Interconversions of Vitamin A Derivatives
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The kinetics of the I2-catalyzed isomerization of the retinal isomers were studied.The all-trans isomer formed 13-cis-retinal rapidly with a rate constant 1.9E-4 s-1.The reverse reaction occurred with a rate constant of 4.5E-4 s-1.The 11-cis isomer was first converted to all-trans-retinal with a rate constant of 3.1E-4 s-1, although the 13-cis isomer was also rapidly formed.The 9-cis isomer was isomerized to the 9-cis, 13-cis isomer before the other isomers were generated and the 13-cis isomer was converted to its all-trans congener prior to the formation of the other isomers.Similar results appear to occur when other methods of catalysis are used.This isomerization about the C13-C14 double bond appears to be kinetically favored event, eliminating the possibility that 11-cis might be a kinetic product formed from the all-trans isomer.At equilibrium, only 0.1percent of 11-cis-retinal is found.Equilibration of all-trans-retinol palmitate also generated very little of the 11-cis-isomer (/= 0.2percent) 11-cis-retinol palmitate at equilibrium.The implications of these results for an 11-cis-retinal regeneration mechanism in the eye are discussed.
- Rando, Robert R.,Chang, Andrew
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p. 2879 - 2882
(2007/10/02)
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- Transient Phenomena in the Pulse Radiolysis of Retinyl Polyenes. 1. Radical Anions
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The spectra and kinetics of formation and decay of radical anions of a number of retinyl polyenes have been studied in methanol and 2-propanol at room temperature, using pulse radiolysis and kinetic spectrophotometry.The bimolecular rate constants for the attachment of solvated electrons, e-MeOH, to the retinyl polyenes are in the diffusion-controlled limit (8.6 x 109-1.6 x 1010 M-1 s-1).The radical anions of retinol and retinol acetate have their spectral maxima at 370-390 nm, and undergo decay very slowly with second-order kinetics.On the other hand, the radical anions of retinal, retinal n-butylamine Schiff base, and retinoic acid/ester have spectral maxima at 430-510 nm, and decay by first-order kinetics in methanol with rate constants in the range 1 x 104-1 x 106 s-1.The decay rates of radical anions of retinal and retinoic acid/ester become considerably longer on going from methanol to less acidic alcohol, 2-propanol, suggesting that protonation by solvent is the major mode of their decay in protic media.In the case of retinal Schiff base, an additional slow process with bimolecular rate constant 9.0 x 107 M-1 s-1 im methanol is observed for the formation of radical anion and is ascribed to the electron-transfer reaction from the methanol radical, .CH2OH.
- Raghavan, N.V.,Das, P.K.,Bobrowski, K.
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p. 4569 - 4573
(2007/10/02)
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