- A-B-A-B-A block amphiphiles. Balance between hydrophilic and hydrophobic segmentation
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Six penta-block amphiphiles of the general structure A-B-A-B-A or B-A-B-A-B (where A = a hydrophilic ether and B = a hydrophobic carbon chain) were synthesized and examined via water solubilities, surface activities, cloud points, and self-diffusion coeff
- Menger, Fredric M.,Lu, Hao,Lundberg, Dan
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- Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
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We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug-target complex. Thus, we designed ligand-phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand-phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.
- Kawamura, Shuhei,Ito, Yoshihiko,Hirokawa, Takatsugu,Hikiyama, Eriko,Yamada, Shizuo,Shuto, Satoshi
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supporting information
p. 4020 - 4029
(2018/05/07)
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- Highly efficient synthesis of monodisperse poly(ethylene glycols) and derivatives through macrocyclization of oligo(ethylene glycols)
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A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs. Macrocycles make synthesis easier: Convenient macrocyclization of the OEGs provides versatile macrocyclic sulfates. These compounds are cornerstones for both monofunctionalization of OEGs and highly efficient synthesis of monodisperse PEGs and derivatives, including an unprecedented 64-mer.
- Zhang, Hua,Li, Xuefei,Shi, Qiuyan,Li, Yu,Xia, Guiquan,Chen, Long,Yang, Zhigang,Jiang, Zhong-Xing
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p. 3763 - 3767
(2015/03/18)
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- Synthesis and the structure to property relationship of monoperfluoroalkyl polyethylene glycol
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Monoprotected polyethylene glycols (PEG) react with epichlorohydrin to furnish PEGylated epoxides. The latter were converted into the corresponding α-(2-F-alkylethyl)thiomethyl polyethylene glycols by treatment with 2-F-alkylethanethiol. Surface activity
- Jaoued-Grayaa, Najeh,Boughariou-Charrada, Boutheina,Hedhli, Ahmed
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p. 767 - 772
(2014/07/08)
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- HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING SAID COMPOUNDS, USE THEREOF AND PROCESSES FOR THE PREPARATION THEREOF
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The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.
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Page/Page column 35; 36
(2013/07/05)
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- OLIGOMER CONJUGATES OF LIDOCAINE AND ITS DERIVATIVES
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The invention provides small molecule drugs that are chemically modified by covalent attachment of a water-soluble oligomer.
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Page/Page column 41; 46
(2009/05/30)
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- GALACTOSE DERIVATIVE, DRUG CARRIER AND MEDICINAL COMPOSITION
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The object of the invention is to provide a novel and useful galactose derivative constituting a drug carrier by which a medicine can be efficiently transferred into the liver, a drug carrier comprising the derivative, and a pharmaceutical composition comprising the carrier and a medicine. The present invention relates to a galactose derivative made up of galactose, a suitable spacer and a certain lipid, a drug carrier comprising the derivative and a cationic lipid, and a pharmaceutical composition comprising the carrier and a medicine (preferably a double strand RNA, a double strand DNA, an oligo nucleic acid) .
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Page/Page column 23
(2010/11/27)
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- Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor
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Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains.
- Tahtaoui, Chouaib,Parrot, Isabelle,Klotz, Philippe,Guillier, Fabrice,Galzi, Jean-Luc,Hibert, Marcel,Ilien, Brigitte
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p. 4300 - 4315
(2007/10/03)
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- Synthesis of taxoids with improved cytotoxicity and solubility for use in tumor-specific delivery
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To develop effective taxane-antibody immunoconjugates, we have prepared a series of modified taxanes that have both improved toxicity and solubility in aqueous systems as compared to paclitaxel (1a). These taxanes have been modified at either the C-10 or
- Miller, Michael L.,Roller, Elizabeth E.,Zhao, Robert Y.,Leece, Barbara A.,Ab, Olga,Baloglu, Erkan,Goldmacher, Victor S.,Chari, Ravi V. J.
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p. 4802 - 4805
(2007/10/03)
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- Multigram Synthesis of Well-Defined Extended Bifunctional Polyethylene Glycol (PEG) Chains
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A series of novel, well-defined, unsymmetrical poly(ethylene glycol) chains of the type X(OCH2-CH2)nY (where X = protecting group; Y = nucleofuge or a different protecting group; n = 3, 6, 9, 12, 15, 18, and 24) were prepared in high yields by applying orthogonal protecting groups. The purity of the compounds was fully verified by elemental and high-resolution mass spectrometry analyses.
- Loiseau, Francois A.,Hii, King Kuok,Hill, Alison M.
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p. 639 - 647
(2007/10/03)
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- Design, synthesis, and activity of membrane-disrupting bolaphiles
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Four new classes of bolaphiles ("double-headed" single-chain surfactants) have been prepared, via condensation of an homologous series of linear saturated, olefinic, and acetylenic α,ω-dicarboxylic acids with hexaethylene glycol, and evaluated for their ability to induce the release of 5(6)-carboxyfluorescein (CF) entrapped within large unilamellar vesicles derived from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Operationally, the membrane-disrupting activity of the bolaphiles has been found to vary by a factor of ca. 100, when the total number of carbon atoms which separate the carboxylate moieties range from 12 to 24; the most active bolaphile is approximately three times more active than Triton X-100. When the affinity of the bolaphiles toward POPC membranes is considered, the intrinsic membrane-disrupting activity varies by a factor of ca. 230. A "loop" model is proposed to account for the general trends in bolaphile activity that are observed, where the depth of loop penetration and loop width are presumed to be the key factors involved in determining membrane-disrupting activity. The potential utility of these surfactants as antimicrobial agents, and as anti-HIV agents in particular, is briefly discussed.
- Jayasuriya, Nimal,Bosak, Stanislav,Regen, Steven L.
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p. 5844 - 5850
(2007/10/02)
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