- A, C; A',C'-DOUBLY CAPPED β-CYCLODEXTRIN. DIRECT EVIDENCE FOR THE CAPPING STRUCTURE
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Doubly capped β-cyclodextrin was firstly prepared in good yield by the treatment of β-cyclodextrin with an excess amount (2.6/1 mol/mol) of benzophenone-3,3'-disulfonyl chloride.This successful double capping demonstrates that benzophenone-3,3'-disulfonyl capping takes place on A, C rings.The present double cap is a useful key intermediate for the preparation of regiospecifically tetrasubstituted cyclodextrins.
- Tabushi, Iwao,Yuan, Lung Chi,Shimokawa, Kazuhiro,Yokota, Kan-ichi,Mizutani, Tadashi,Kuroda, Yasuhisa
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- Targeted delivery of pharmacological chaperones for Gaucher disease to macrophages by a mannosylated cyclodextrin carrier
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Gaucher disease (GD) is a rare monogenetic disorder leading to dysfunction of acid β-glucosidase (β-glucocerebrosidase; GCase) and accumulation of glucosylceramide in lysosomes, especially in macrophages (Gaucher cells). Many of the mutations at the origin of GD do not impair the catalytic activity of GCase, but cause misfolding and subsequent degradation by the quality control system at the endoplasmic reticulum. Pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the endogenous mutant enzyme represent promising alternatives to the currently available enzyme replacement and substrate reduction therapies (ERT and SRT, respectively), but unfavorable biodistribution and potential side-effects remain important issues. We have now designed a strategy to enhance the controlled delivery of PCs to macrophages that exploit the formation of ternary complexes between the PC, a trivalent mannosylated β-cyclodextrin (βCD) conjugate and the macrophage mannose receptor (MMR). First, PC candidates with appropriate relative avidities towards the βCD cavity and the GCase active site were selected to ensure efficient transfer of the PC cargo from the host to the GCase active site. Control experiments confirmed that the βCD carrier was selectively recognized by mannose-specific lectins and that the corresponding PC:mannosylated βCD supramolecular complex retained both the chaperoning activity, as confirmed in human GD fibroblasts, and the MMR binding ability. Finally, fluorescence microscopy techniques proved targeting and cellular uptake of the PC-loaded system in macrophages. Altogether, the results support that combined cyclodextrin encapsulation and glycotargeting may improve the efficacy of PCs for GD. This journal is
- Rodriguez-Lavado, Julio,De La Mata, Mario,Jimenez-Blanco, Jose L.,Garcia-Moreno, M. Isabel,Benito, Juan M.,Diaz-Quintana, Antonio,Sanchez-Alcazar, Jose A.,Higaki, Katsumi,Nanba, Eiji,Ohno, Kousaku,Suzuki, Yoshiyuki,Ortiz Mellet, Carmen,Garcia Fernandez, Jose M.
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- Evidence of a self-inclusion phenomenon for a new class of mono-substituted alkylammonium-β-cyclodextrins
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A new class of mono-substituted N-alkyl-N, N-dimethylammonium-β- cyclodextrins has been synthesized in a three step procedure from the native β-cyclodextrin. The structural analysis of these compounds undertaken by combined use of 1D and 2D NMR spectra indicate that the two methyl groups bound on the nitrogen are magnetically inequivalent due to a self-inclusion phenomenon of the alkyl chain inside the CD cavity. A variable-temperature 1H NMR study showed that these mono-substituted CD derivatives formed temperature-independent intramolecular complexes with their own alkylammonium substituent. The strength of the interaction between the alkyl moiety and the cyclodextrin cavity has been evaluated by a competitive method using an adamantane derivative. Finally, surface tension measurements demonstrated the surface active character of these compounds and confirmed their self-inclusion ability. The Royal Society of Chemistry 2005.
- Binkowski, Cecile,Hapiot, Frederic,Lequart, Vincent,Martin, Patrick,Monflier, Eric
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- Synthesis of monocationic β-cyclodextrin derivatives
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Reactions of 6-bromo- and 6-iodo-6-deoxy-β-cyclodextrin with organic amines of diverse nature afforded a series of monocationic derivatives with aminium groups located in the cyclodextrin scaffold on the side of the primary hydroxy groups. The structure a
- Shipilov,Kurochkina,Levina,Malenkovskaya,Grachev
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- Cyclodextrin-based polymers for therapeutics delivery
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The present invention relates to novel compositions of therapeutic cyclodextrin containing polymeric compounds designed as a carrier for small molecule therapeutics delivery and pharmaceutical compositions thereof. These cyclodextrin-containing polymers i
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Page/Page column 66; 67
(2017/02/28)
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- COMPLEXING AGENTS FOR COMPOSITIONS CONTAINING INCLUSION COMPLEXES
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The invention provides a composition containing particulate composite of a polymer and a therapeutic agent. The composition also contains a complexing agent. The polymer interacts with the complexing agent in a host-guest or a guest-host interaction to fo
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Paragraph 0164; 0165
(2017/03/21)
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- Solubility enhancement of flavonols in the inclusion complex with thioether-bridged dimeric β-cyclodextrins
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Dimeric β-cyclodextrin linked by a thioether bridge was synthesized from a reaction of mono-6-iodo-6-deoxy- β-cyclodextrin with sodium sulfide, and the structure was analyzed using nuclear magnetic resonance spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The effects of thioether-bridged dimeric β-CD on the aqueous solubility of flavonols (myricetin, quercetin, and kaempferol) were investigated by ultraviolet-visible spectroscopy. The aqueous solubility of myricetin, quercetin, and kaempferol were enhanced 33.6-, 12.4-, and 10.5-fold following the addition of 9 mM of thioether-bridged dimeric β-CD. In comparison, the aqueous solubility of myricetin, quercetin, and kaempferol were enhanced 5.4-, 3.3-, and 2.7-fold using the same concentration of monomeric β-cyclodextrin. Furthermore, the formation of flavonol/thioether-bridged dimeric β-CD inclusion complexes was confirmed with nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The results showed that the nature of the complexes significantly differed from that of free flavonols. Herein, we suggest that the thioether-bridged dimeric β-CD can act as an effective complexing agent for flavonols.
- Cho, Eunae,Jeong, Daham,Paik, Hyun-Dong,Jung, Seunho
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p. 2487 - 2493
(2014/12/10)
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- Intermolecular interactions between doxorubicin and β-cyclodextrin 4-methoxyphenol conjugates
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Newly synthesized derivatives of β-cyclodextrin, mono(6-deoxy-6-(1-1, 2,3-triazo-4-yl)-1-propane-3-O-(4-methoxyphenyl))β-cyclodextrin (1) and mono(6-deoxy-6thio(1-propane-3-O-(4-methoxyphenyl))) β-cyclodextrin (2) were designed to be receptors of the anticancer drug doxorubicin, which could potentially decrease the adverse effects of the drug during treatment. In both aqueous and aqueous dimethyl sulfoxide (DMSO) solutions, doxorubicin forms an inclusion complex with the new cyclodextrin derivatives with formation constants of Ks = 2.3 × 104 and Ks = 3.2 × 105 M-1 for cyclodextrins 1 and 2, respectively. The stabilities of the complexes are 2-3 orders of magnitude greater than those with native β-cyclodextrin, and the flexibility of the linker of the side group of the cyclodextrins contributes to this stability. In a hydrogen-bond- accepting solvent, such as pure DMSO, an association that includes hydrogen bonding and chloride ions is favored over the binding of doxorubicin in the cavity of the cyclodextrin derivative. This contrasts with an aqueous medium in which a strong inclusion complex is formed. Cyclic voltammetry, UV-vis, 1H NMR, and molecular modeling studies of solutions in DMSO and of solutions in water/DMSO demonstrated that the two different modes of intermolecular interaction between doxorubicin and the cyclodextrin derivative depended on the solvent system being utilized.
- Swiech, Olga,Mieczkowska, Anna,Chmurski, Kazimierz,Bilewicz, Renata
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experimental part
p. 1765 - 1771
(2012/05/20)
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- SUPRAMOLECULAR COMPLEXES CONTAINING THERAPEUTIC AGENTS
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A method of preparing a supramolecular complex containing at least one therapeutic agent and a multi-dimensional polymer network is described. A supramolecular complex prepared by a method of the invention is described. A method of treatment by administer
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Page/Page column 33
(2010/11/26)
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- Cyclodextrin-grafted poly(phenylene ethynylene) with chemically-responsive properties
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Water-soluble poly(phenylene ethynylene) carrying β-cyclodextrin was prepared; the polymer exhibited a fluorescence color change or quenching, depending on the kind of guest. The Royal Society of Chemistry 2006.
- Ogoshi, Tomoki,Takashima, Yoshinori,Yamaguchi, Hiroyasu,Harada, Akira
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p. 3702 - 3704
(2007/10/03)
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- β-Cyclodextrin dimers as potential tumor pretargeting agents
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A β-cyclodextrin dimer binds a di-tert-butylbenzyl-Cucyclen with high affinity, demonstrating potential as a receptor/ligand system for tumor pretargeting with monoclonal antibodies.
- Edwards,Reichert,D'Avignon,Welch
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p. 1312 - 1313
(2007/10/03)
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- Mono-β-cyclodextrin as an Efficient Glyoxalase Mimic
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Trifunctional mono-β-cyclodextrin (MACD) has been prepared and used as a gloxalase model.When 2-naphthylglyoxal (NAGO) is employed as a diagnostic substrate, MACD shows an overall activity greater than the reference compo
- Tamagaki, Seizo,Katayama, Atsushi,Maeda, Masahiko,Yamamoto, Noritaka,Tagaki, Waichiro
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p. 507 - 512
(2011/08/10)
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- Dynamic Molecular Motions of p-Methylcinnamic Acid Included into β-Cyclodextrin derivatives: A New Type of Free-energy Relationship in Complex Formation
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The deuterium quadrupolar relaxation times of (E)--p-methylcinnamic acid (G) included into various β-cyclodextrin derivatives have been measured by line-shape analysis.The association constants for the complexation of host with (G) are largely affected by additional recognition elements substituted into the parent β-cyclodextrin.The correlation times for the molecular motion of (G) which have been estamited from the corresponding relaxation times are also greatly affected by these additional recognition elements.Thus, the relationship between the association constants and the correlation times of (G) may be desscribed simply in the present case, i.e., the host molecule having the larger association constant restricts the molecular motion of (G) more significantly.One exception is 6,6'-dideoxy-6,6'-di-iodo-β-cyclodextrin (CDI2) which has a large association constant but restricts only slightly the molecular motion of (G).The observed large association constant and the small correlation time for CDI2 are reasonably interpreted in terms of the effect of the large polarizability of iodine.The free-energy relationship between the binding process and the molecular motion of (G) is discussed on the basis of these new observations.
- Kuroda, Yasuhisa,Yamada, Masahiko,Tabushi, Iwao
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p. 1409 - 1416
(2007/10/02)
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