- Nucleic acid medicine delivery system and application thereof
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The invention discloses a nucleic acid medicine delivery system and application thereof. The system consists of a neutral base lipid carrier and metal salt, wherein the structure of the neutral base lipid carrier is shown as a formula I. In addition, the delivery system provided by the invention also comprises metal salt. The experiment proves that through the existence of metal ion, the silent activity of the nucleic acid medicine can be effectively improved; the effective transportation of the nucleic acid medicine in the cells and in the body can be realized. The chemical modification methods such as D,L-isonucleoside modification, deoxyinosine modification, peptide conjugation modification and phosphorylation modification are jointly used for nucleic acid delivery system study; the advantages and rules of the nucleic acid delivery in a composite modification mode are sufficiently explored; the modification strategies are used in the nucleic acid medicine study. Study proves that the products obtained through chemical modification are more applicable to the system; in addition, the advantages of stable physicochemical properties, good bioactivity and good membrane permeability and the like are realized. The nucleic acid medicine delivery system provided by the invention has wide application prospects in the gene treatment field. The formula is shown in the description.
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Paragraph 0053; 0057; 0078
(2018/09/21)
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- Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation
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Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.
- Mallik, Suman,Prasad, Ramesh,Bhattacharya, Anindita,Sen, Prosenjit
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supporting information
p. 434 - 439
(2018/05/23)
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- Lipid-modified oligonucleotide conjugates: Insights into gene silencing, interaction with model membranes and cellular uptake mechanisms
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The ability of oligonucleotides to silence specific genes or inhibit the biological activity of specific proteins has generated great interest in their use as research tools and therapeutic agents. Unfortunately, their biological applications meet the limitation of their poor cellular accessibility. Developing an appropriate delivery system for oligonucleotides is essential to achieve their efficient cellular uptake. In the present work a series of phosphorothioate lipid–oligonucleotide hybrids were synthesized introducing covalently single or double lipid tails at both 3′- and 5′-termini of an antisense oligonucleotide. Gene transfections in cultured cells showed antisense luciferase inhibition without the use of a transfecting agent for conjugates modified with the double-lipid tail at 5′-termini. The effect of the double lipid-tailed modification was further studied in detail in several model membrane systems as well as in cellular uptake experiments. During these studies the spontaneous formation of self-assembled microstructures is clearly observed. Lipidation allowed the efficient incorporation of the oligonucleotide in HeLa cells by a macropinocytosis mechanism without causing cytotoxicity in cells or altering the binding properties of the oligonucleotide conjugates. In addition, both single- and double-tailed compounds showed a similar behavior in lipid model membranes, making them useful in nucleotide-based technologies.
- Ugarte-Uribe, Bego?a,Grijalvo, Santiago,Pertí?ez, Samuel Nú?ez,Busto, Jon V.,Martín, César,Alagia, Adele,Go?i, Félix M.,Eritja, Ramón,Alkorta, Itziar
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supporting information
p. 175 - 186
(2016/12/23)
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- Cooperative Activation of Cobalt–Salen Complexes for Epoxide Hydration Promoted on Flexible Porous Organic Frameworks
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Developing solid catalysts with multiple active sites working cooperatively is desirable for efficient chemical transformations. However, most solid catalysts are rigid and impede the cooperation between their spatially isolated active sites. Two flexible porous organic frameworks (POFs) with integrated Co(salen) as active sites have been successfully synthesized for mimicking the cooperative modes of enzymes. The POFs exhibit second-order rate dependence on Co(salen) concentration in the network and afford much higher TOF (3300 versus 2670 h?1) than the homogeneous counterpart in the hydration of propylene epoxide. POFs with a flexible network thus not only facilitate but also enhance the cooperation of nearby Co(salen). Moreover, POFs could catalyze oversized substrates, have a wide substrate scope, and exhibit high stability.
- Zhong, Mingmei,Li, He,Chen, Jian,Tao, Lin,Li, Can,Yang, Qihua
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supporting information
p. 11504 - 11508
(2017/08/30)
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- Total Synthesis of the Bis-silyl Ether of (+)-15-epi-Aetheramide A
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Synthesis of the macrolactone depsipeptide aetheramide A was attempted by three different approaches. The first approach to form the macrolactone involving macrolactonization to form the C1-C21 bond and the second approach using a ring-closing metathesis (RCM) strategy to form the C10-C11 olefinic bond failed. The third approach starting from R-mandelic acid, involving the RCM reaction to install the C18-C19 ring junction, was successful in assembling the macrolactone.
- Revu, Omkar,Prasad, Kavirayani R.
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p. 438 - 460
(2017/04/26)
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- Supramolecular assemblies of novel aminonucleoside phospholipids and their bonding to nucleic acids
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A novel class of aminonucleoside phospholipids has been developed. These molecules could spontaneously assemble into supramolecular structures including multilamellar organization, hydrogels, superhelical strands, and vesicles. Their ability to bind to DNA by hydrogen bonding and π-π stacking interactions was investigated by many means. This journal is
- Pan, Delin,Sun, Jing,Jin, Hongwei,Li, Yating,Li, Liyu,Wu, Yun,Zhang, Lihe,Yang, Zhenjun
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supporting information
p. 469 - 472
(2015/02/19)
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- MELANIN PRODUCTION INHIBITOR
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Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor is represented by general formula (1) (excluding clotrimazole) and/or a pharmacologically acceptable salt thereof. In the formula, A1, A2 and A3 are independently selected from a hydrogen atom, an aryl group which may have a substituent, and an aromatic heterocyclic group which may have a substituent. At least one of A1, A2 and A3 is selected from the aryl group and the aromatic heterocyclic group, the total number of carbon atoms contained in A1, A2 and A3 is 6 to 50 and, when at least two of A1, A2 and A3 represent the aryl groups or the aromatic heterocyclic groups, the adjacent two aryl or aromatic heterocyclic groups may be bound to each other via an alkyl chain or an alkenyl chain to form a ring; m represents an integer of 0 to 2; X represents a hetero atom, a hydrogen atom, or a carbon atom; R1 and R2 are independently selected from a hydrogen atom and an oxo group. When one of R1 and R2 is an oxo group, the other is not present. R3 is selected from a hydrogen atom, and a C1-8 hydrocarbon group in which one or some of hydrogen atoms or carbon atoms may be substituted by a hetero atom or hetero atoms. The number of R3's present in the compound corresponds to X and, when two or more R3's are present, the R3's are independently present and the adjacent two R3's may be bound to each other to form, together with X, a ring, and the terminal of R3 may be bound to a carbon atom to which A1, A2 and A3 are bound, thereby forming a ring.
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Paragraph 0331 - 0334
(2015/12/17)
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- Smart tools and orthogonal click-like reactions onto small unilamellar vesicles
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Abstract Click-based reactions were conducted at the surface of small unilamellar vesicles (SUVs) to provide onto-vesicle chemistry with efficient innovative ready-for-use tools. For that purpose, four amphiphilic molecules were designed to insert into bi
- Salomé, Christophe,Spanedda, Maria Vittoria,Hilbold, Benoit,Berner, Etienne,Heurtault, Béatrice,Fournel, Sylvie,Frisch, Benoit,Bourel-Bonnet, Line
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- Total synthesis of bafilomycin A1
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A convergent synthesis of bafilomycin A1, a potent inhibitor of V-type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium-catalyzed trans-reduction of the resulting propargylic enyne efficiently installs the required C10-C13 trans,trans-diene subunit, implementing an alternative strategy to traditional palladium-catalyzed cross-coupling strategies. A highly selective oxidation of a secondary hydroxyl group in a triol sets the stage for the completion of the synthesis. Copyright
- Kleinbeck, Florian,Fettes, Gabriela J.,Fader, Lee D.,Carreira, Erick M.
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supporting information; experimental part
p. 3598 - 3610
(2012/05/04)
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- Chiral nanoporous metal-metallosalen frameworks for hydrolytic kinetic resolution of epoxides
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Chiral nanoporous metal-organic frameworks are constructed by using dicarboxyl-functionalized chiral Ni(salen) and Co(salen) ligands. The Co(salen)-based framework is shown to be an efficient and recyclable heterogeneous catalyst for hydrolytic kinetic resolution (HKR) of racemic epoxides with up to 99.5% ee. The MOF structure brings Co(salen) units into a highly dense arrangement and close proximity that enhances bimetallic cooperative interactions, leading to improved catalytic activity and enantioselectivity in HKR compared with its homogeneous analogues, especially at low catalyst/substrate ratios.
- Zhu, Chengfeng,Yuan, Guozan,Chen, Xu,Yang, Zhiwei,Cui, Yong
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supporting information; experimental part
p. 8058 - 8061
(2012/07/14)
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- Simple approach to 1-O-protected (R)- and (S)-glycerols from l- and d-arabinose for glycerol nucleic acids (GNA) monomers research
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5-O-Protected (-Tr, -Sitert-BuPh2) d- and l-arabinofuranoses easily available in multigram quantities were converted to (S)- and (R)-1-O-protected glycerols, respectively, via oxidation (NaIO4) and reduction (NaBH4). Sourc
- Doboszewski, Bogdan,Herdewijn, Piet
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p. 3853 - 3855
(2011/08/06)
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- A mild and efficient method for the chemoselective deprotection of acetonides with lanthanum(III) nitrate hexahydrate
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Acetonides are hydrolyzed selectively and efficiently with lanthanum(III) nitrate hexahydrate in acetonitrile. The method has good compatibility with other sensitive hydroxyl protecting groups such as trityl, TBDMS, THP, OAc, OBz and OBn.
- Malla Reddy,Venkat Reddy,Venkateswarlu
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p. 7439 - 7441
(2007/10/03)
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- Efficient method for selective cleavage of acetals and ketals using peroxymonosulfate on alumina under solvent-free conditions
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In an environmentally benign solvent-free system, acetals and ketals are rapidly cleaved with peroxymonosulfate-alumina under microwave irradiation in high yields.
- Bose, D. Subhas,Jayalakshmi,Narsaiah, A. Venkat
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- A new approach to the stereospecific synthesis of phospholipids. The use of L-glyceric acid for the preparation of diacylglycerols, phosphatidylcholines, and related derivatives
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A new stereospecific synthesis of phospholipid derivatives of 1,2- diacyl-sn-glycerols is reported. The synthesis is based on (1) the use of L- glyceric acid as the stereocenter for construction of the optically active phospholipid molecule, (2) preparation of 3-triphenylmethyl-sn-glycerol as the key intermediate for sequential introduction of the primary and secondary acyl functions leading to the chiral diglycerides, and (3) elaboration of the sn-3-phosphodiester headgroup via phosphorylation using 2-chloro-2-oxo-1,3,2- dioxaphospholane, followed by ring opening of the five-membered phosphorus heterocycle with trimethylamine, ammonia, as well as oxygen and sulfur nucleophiles. The sequence has been shown to be suitable for the preparation of both symmetric and mixed-chain diacylglycerols with saturated and unsaturated acyl substituents. Phospholipid headgroups including phosphocholine, phosphoethanolamine, phosphoethanol, and phosphoethylthioacetate functions have been prepared. Application of the method to the synthesis of functionalized phosphatidylcholines has also been demonstrated by incorporating spectroscopically active spin-labeled and fluorescent reporter groups via postsynthetic derivatization of chain terminal ω-aminoalkyl functions of the acyl substituents of the compounds. The synthetic methods developed have a great deal of flexibility, providing convenient routes to a wide range of structurally variable phospholipids for physicochemical, enzymological, and cell-biological studies.
- Roodsari, Farzaneh S.,Wu, Dongpei,Pum, Gregory S.,Hajdu, Joseph
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p. 7727 - 7737
(2007/10/03)
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- A metal-chelating lipid for 2D protein crystallization via coordination of surface histidines
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Two-dimensional protein crystallization on lipid monolayers is becoming a powerful technique for structure determination as well as materials applications. However, progress has been hindered by the requirement of a unique affinity lipid for each new protein of interest. Metal ion coordination by surface-accessible histidine side chains provides a convenient and general method for targeting of proteins to surfaces. Here we present the synthesis and characterization of a metal-chelating lipid which has been designed to target proteins to Langmuir monolayers and promote their two-dimensional crystallization based on histidine coordination. The lipid utilizes the metal chelator iminodiacetate (IDA) as the hydrophilic headgroup and contains unsaturated, oleyl tails to provide the fluidity necessary for two-dimensional protein crystallization. The lipid is shown to bind copper from the subphase strongly when incorporated in Langmuir monolayers. In addition, it is possible to form copper-containing monolayers by spreading the premetalated lipid on the subphase in the absence of copper. Fluorescence microscopy reveals the binding and crystallization of the protein streptavidin, promoted by the simultaneous coordination of two surface-accessible histidine side chains to the IDA-Cu lipid.
- Pack, Daniel W.,Chen, Guohua,Maloney, Kevin M.,Chen, Chao-Tsen,Arnold, Frances H.
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p. 2479 - 2487
(2007/10/03)
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- Large scale monotritylations of water soluble compounds containing multiple hydroxyl groups
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A procedure for the large scale monotritylation of watersoluble substrates containing multiple hydroxylgroups is reported; no elaborate purification procedures are required.
- Kaats-Richters,Zwikker,Keegstra,Jenneskens
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p. 2399 - 2409
(2007/10/02)
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- Synthesis and Ruthenium-Catalyzed Enantioselective Hydrogenation of 3-O-Substituted 1,3-dihydroxypropan-2-ones
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A number of 3-O-substituted 1,3-dihydroxypropan-2-ones have been synthesized in view of their potential use as prochiral precursors of optically active glycerols.Indeed, the oxo-ethers have been reduced to the corresponding 3-O-substituted glycerols via c
- Cesarotti, Edoardo,Antognazza, Patrizia,Pallavicini, Marco,Villa, Luigi
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p. 2344 - 2349
(2007/10/02)
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- A novel class of platelet activating factor (PAF) antagonists. II. Modification of the 2-position of the glycerol backbone of PAF-sulfonamide isosteres
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In a continuing effort to obtain more potent platelet activating factor (PAF) antagonists, we tried to synthesize a series of PAF-sulfonamide isosteres in which the substituent at the 2-position was modified to an acetoxy equivalent other than the methoxy group. These modifications produced highly active PAF antagonists. Compound 3-[2-(5-methyl-2H-tetrazol-2-yl)-3-(octadecylcarbamoyloxy)propylaminosu lfonyl]propylquinolinium iodide (52) showed the most potent activity in the in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma (IC50 = 125 nm) and also in the in vivo protective effect on PAF-induced lethality in mice, with prolonged duration of action. Optically active enantiomers of this compound were synthesized and the (S)-(-)-isomer (IC50 = 87 nM) was found to be three times more potent that the (R)-(+)-isomer (IC50 = 289nM), clearly exemplifying the enantioselectivity in the PAF-antagonist action of this novel compound.
- Tsuri,Matsui,Haga,Kamata,Haghishita,Takahashi,Kakushi,Uchida,Katakeyama,Kurosawa
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- SYNTHESIS AND CHARACTERIZATION OF 1-O-β-LACTOSYL-(R,S)-GLYCEROLS AND 1,3-DI-OΒ-LACTOSYLGLYCEROL
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The synthesis of 1-O-β-lactosyl-(R,S)-glycerols was achieved by three methods: (a) in 25percent yield by the trimethylsilyl trifluoromethanesulfonate-promoted reaction of octa-O-acetyl-β-lactose (11) with ca. 0.5 mol-equiv. of 2-O-benzylglycerol (4), (b)
- Hronowski, Lucjan J. J.,Szarek, Walter A.,Hay, George W.,Krebs, Anita,Depew, William T.
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p. 203 - 218
(2007/10/02)
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- Glycerol ether phosphatides
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Compounds of the general formula STR1 wherein two of the residues R1, R2 and R3 represent C10-30 -alkyl residues with at least 8 C-atoms in a straight chain, at least one of these residues being substituted by a
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- Chemistry of the lipids - X. Synthesis of optically active α,β-diglycerides
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1. A. new route for the synthesis of optically active α,β-diglycerides has been developed. 2. D- and L-α, β-Distearins and D-α, β-dilinolenin have been synthesized from the readily accessible L- and D-α-O-tritylglycerols.
- Molotkovskii,Nikulina,Bergel'son
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p. 179 - 181
(2007/10/13)
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