604-35-3Relevant articles and documents
Orientation of fluorinated cholesterol in lipid bilayers analyzed by 19F tensor calculation and solid-state NMR
Matsumori, Nobuaki,Kasai, Yusuke,Oishi, Tohru,Murata, Michio,Nomura, Kaoru
, p. 4757 - 4766 (2008)
6-F-cholesterol was reported to exhibit biological and interfacial properties similar to unmodified cholesterol. We have also found that 6-F-cholesterol mimicked the cholesterol activity observed in the systems of amphotericin B and lipid rafts. However, to use 6-F-cholesterol as a molecular probe to explore molecular recognition in membranes, it is indispensable to have detailed knowledge of the dynamic and orientation properties of the molecule in membrane environments. In this paper, we present the molecular orientation of 6-F-cholesterol (30 mol %) in dimyristoylphosphatidylcholine (DMPC) bilayers revealed by combined use of 19F chemical shift anisotropy (CSA), 2H NMR, and C-F rotational echo double resonance (REDOR) experiments. The axis of rotation of 6-F-cholesterol was shown to be in a similar direction to that of cholesterol in DMPC bilayers, which is almost parallel to the long axis of the molecular frame. The molecular order parameter of 6-F-cholesterol was determined to be ca. 0.85, which is within the range of reported values of cholesterol. These findings suggest that the dynamic properties of 6-F-cholesterol in DMPC are quite similar to those of unmodified cholesterol; therefore, the introduction of a fluorine atom at C6 has virtually no effect on cholesterol dynamics in membranes. In addition, this study demonstrates the practical utility of theoretical calculations for determining the 19F CSA principal axes, which would be extremely difficult to obtain experimentally. The combined use of quantum calculations and solid-state 19F NMR will make it possible to apply the orientation information of 19F CSA tensors to membrane systems.
Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions
Dordick, Jonathan S.,Fu, Li,Fuster, Mark M.,Grant, Oliver C.,Jin, Weihua,Kim, So Young,Linhardt, Robert J.,Montgomery, David W.,Sood, Amika,Woods, Robert J.,Zhang, Fuming
, (2020)
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681–686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453–459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.
Site-selective and metal-free aliphatic C-H oxidation enabled synthesis of [5,24,25-d3]-(25s)-δ7-dafachronic acid
Liu, Weilong,Li, Xiangke,Chen, Jie,Li, Tiemei,Dong, Mengqiu,Lei, Xiaoguang
, p. 5345 - 5349 (2015)
Steroid hormones play significant roles in both worms and mammalians. (25S)-Δ7-Dafachronic acid (Δ7-DA, 1) is a member of the dafachronic acid hormonal series that regulates both development and lifespan of C. elegans. Despite its importance, effective tools for the illumination of its mode of action are lacking. Herein, we report an efficient synthesis of trideuterated Δ7-DA, [5,24,25-D3]-(25S)-Δ7-dafachronic acid ([D3]-Δ7-DA, 2), as a useful chemical tool for subsequent biological studies. Key steps for this bioinspired synthesis approach include site-selective aliphatic C-H oxidation mediated by methyl(trifluoromethyl)dioxirane (TFDO), and the iridium/phosphine-oxazoline-catalyzed late-stage asymmetric deuterium reduction. Bio is best! [5,24,25-D3]-(25S)-Δ7-Dafachronic acid, an isotope-labeled steroid hormone has been synthesized in 14 steps from cholesterol inspired by biosynthesis. Key steps include a site-selective and metal-free aliphatic C-H oxidation and a late-stage catalytic asymmetric deuteration (see scheme). [5,24,25-D3]-(25S)-Δ7-Dafachronic acid will be severed as an effective chemical tool for the illumination of novel molecular mechanisms of longevity.
IMIDAZOLE MEDIATED ACYLATION OF CHOLESTEROL IN FUNCTIONAL VESICLES: A SIMPLE ANALOGUE OF LECITHIN:CHOLESTEROL ACYLTRANSFERASE
Moss, Robert A.,Bhattacharya, Santanu,Okumura, Yukihisa
, p. 4905 - 4908 (1989)
Imidazole-functionalized surfactants transfer acetyl groups from p-nitrophenyl acetate to cholesterol in vesicular coaggregates.
Novel industrial method for preparing vitamin D3 by taking stigmasterol as raw material
-
, (2021/05/05)
The invention provides a novel industrial method for preparing vitamin D3 by taking stigmasterol as a raw material. The method comprises the following steps: sequentially carrying out hydroxyl acetylation, side chain oxidation, side chain isopentane reduction and hydrogenation on stigmasterol to obtain cholesterol acetate, and then sequentially carrying out oxidation, hydrazone formation, hydrazone removal, hydrolysis, illumination and the like to obtain the vitamin D3. The invention provides a novel method for preparing vitamin D3 from stigmasterol, and the method has the advantages of mild reaction conditions and high yield, and is suitable for industrial production.