17278-74-9Relevant articles and documents
Novel insights into oxidation of fatty acids and fatty alcohols by cytochrome P450 monooxygenase CYP4B1
Thesseling, Florian A.,Hutter, Michael C.,Wiek, Constanze,Kowalski, John P.,Rettie, Allan E.,Girhard, Marco
, (2019/12/12)
CYP4B1 is an enigmatic mammalian cytochrome P450 monooxygenase acting at the interface between xenobiotic and endobiotic metabolism. A prominent CYP4B1 substrate is the furan pro-toxin 4-ipomeanol (IPO). Our recent investigation on metabolism of IPO related compounds that maintain the furan functionality of IPO while replacing its alcohol group with alkyl chains of varying structure and length revealed that, in addition to cytotoxic reactive metabolite formation (resulting from furan activation) non-cytotoxic ω-hydroxylation at the alkyl chain can also occur. We hypothesized that substrate reorientations may happen in the active site of CYP4B1. These findings prompted us to re-investigate oxidation of unsaturated fatty acids and fatty alcohols with C9–C16 carbon chain length by CYP4B1. Strikingly, we found that besides the previously reported ω- and ω-1-hydroxylations, CYP4B1 is also capable of α-, β-, γ-, and δ-fatty acid hydroxylation. In contrast, fatty alcohols of the same chain length are exclusively hydroxylated at ω, ω-1, and ω-2 positions. Docking results for the corresponding CYP4B1-substrate complexes revealed that fatty acids can adopt U-shaped bonding conformations, such that carbon atoms in both arms may approach the heme-iron. Quantum chemical estimates of activation energies of the hydrogen radical abstraction by the reactive compound 1 as well as electron densities of the substrate orbitals led to the conclusion that fatty acid and fatty alcohol oxidations by CYP4B1 are kinetically controlled reactions.
SELECTIVE PYY COMPOUNDS AND USES THEREOF
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Paragraph 0254; 0255; 0256; 0257, (2016/12/12)
The invention relates to PYY compounds having the amino acid in the position corresponding to position 30 of hPYY(1-36) substituted with tryptophan and derivatives thereof with a modifying group attached to the position corresponding to position 7 of hPYY(1-36). The compounds of the invention are selective Y2 receptor agonists. The invention also relates to pharmaceutical compositions comprising such PYY compounds and pharmaceutically acceptable excipients, as well as the medical use of the PYY compounds.
Catalytic hydroxylation in biphasic systems using CYP102A1 mutants
Maurer, Steffen C.,Kuehnel, Katja,Kaysser, Leonard A.,Eiben, Sabine,Schmid, Rolf D.,Urlacher, Vlada B.
, p. 1090 - 1098 (2007/10/03)
Cytochrome P450 monooxygenases are biocatalysts that hydroxylate or epoxidise a wide range of hydrophobic organic substrates. Their technical application is, however, limited to a small number of whole-cell processes. The use of the isolated P450 enzymes is believed to be impractical due to their low stability, stoichiometric need of the expensive cofactor NAD(P)H and low solubility of most substrates in aqueous media. We investigated the behaviour of an isolated bacterial monooxygenase (mutants of CYP102A1) in a biphasic reaction system supported by cofactor recycling with the NADP +-dependent formate dehydrogenase from Pseudomonas sp 101. Using this experimental set-up cyclohexane, octane and myristic acid were hydroxylated. To reduce the process costs a novel NADH-dependent mutant of CYP102A1 was designed. For recycling of NADH an NAD+-dependent FDH was used. The stability of the monooxygenase mutants under the reaction conditions in the biphasic system was quite high as revealed by total turnover numbers of up to 12,850 in the NADPH-dependent cyclohexane hydroxylation and up to 30,000 in the NADH-dependent myristic acid oxidation.
A self-sufficient peroxide-driven hydroxylation biocatalyst
Cirino, Patrick C.,Arnold, Frances H.
, p. 3299 - 3301 (2007/10/03)
Directed evolution of the heme domain of cytochrome P450 BM-3 has resulted in a versatile, highly active peroxide-driven hydroxylation catalyst (see picture) that requires neither NADPH nor reductase and functions in a cell-free reaction system. This simplified, biomimetic catalyst is amenable to further optimization, for example, to improve stability or alter its substrate range.
Process of preparing ω-hydroxy acids
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, (2008/06/13)
A new synthesis of ω-hydroxy acids, which employs commercially available starting materials and lowers the cost of production. The process involves coupling a fatty acyl group by enamine chemistry, followed by a ring expansion and selective reduction of ketoacid.
Asymmetric Syntheses of (R)-(-)-Muscone based on Diastereoselective Conjugate Addition
Ogawa, Tomoyuki,Fang, Cheng-Lin,Suemune, Hiroshi,Sakai, Kiyoshi
, p. 1438 - 1439 (2007/10/02)
(R)-(-)-Muscone was synthesized in a stereocontrolled manner via the stereoselective conjugate addition to a cyclic α,β-unsatureted ester of (R,R)-cyclohexane-1,2-diol accompanied by spontaneous Dieckmann condensation.
Model Studies on the Synthesis of Medium-sized and Large Carbocycles using the Ireland Enolate Claisen Rearrangement
Cameron, Andrew G.,Knight, David W.
, p. 161 - 168 (2007/10/02)
Model studies have shown that the enolate Claisen rearrangement, a modification (developed by R.E.Ireland et al.) of the original Claisen rearrangement, can successfully be applied to the elaboration of medium-sized and large carbocycles from O-silyl enolates of suitable unsaturated macrolides (Scheme).The rearrangements are largely non-stereoselective, a fact which can be rationalised in terms of the intermediacy of both chair- and boat-like transition states and possibly because, in some cases, both the (E)- and (Z)-enolate of the macrolides are involved.
Acides gras marques en position ω par un nucleide radioactif emetteur γ
Riche, Francoise,Mathieu, Jean-Paul,Vincens, Maurice,Bardy, Andre,Comet, Michel,Vidal, Michel
, p. 49 - 55 (2007/10/02)
The synthesis of many saturated, acetylenic, olefinic (Z or E) fatty acids labeled with 123I or 131I at the ω-position has been achieved.The radioactive iodine atom is introduced by a I-, *I- exchange reaction; the influence on the yield of several parameters - presence of iodine carrier, fatty acid and water concentrations, solution acidity - has been studied.Experimental conditions which produce labeling yields higher than 95percent have been defined; these results have lead to a very easy labeling method used in several hospitals in the external study of myocardial metabolism of fatty acids.
ONE-STEP SYNTHESIS OF ω-HYDROXYCARBOXYLIC ACIDS BY THE REACTION OF ω-METALOXYLATED GRIGNARD REAGENTS WITH β-PROPIOLACTONES
Fujisawa, Tamotsu,Mori, Toshiki,Kawara, Tatsou,Sato, Toshio
, p. 569 - 570 (2007/10/02)
ω-Metaloxylated Grignard reagents reacted with β-propiolactones chemo- and regioselectively in the presence of Li2CuCI4 to afford ω-hydroxycarboxylic acids in high yields.
