- Cell transfection with polycationic cyclodextrin vectors
-
Polycationic cyclodextrins (CDs) were complexed with plasmid DNA and their effectiveness as vectors was tested on COS-7 cells. These CDs were modified with pyridylamino, alkylimidazole, methoxyethylamino or primary amine groups at 6-positions of the glucose units. Uncharged CDs, β-CD, hydroxypropyl- β-CD, and dimethyl-β-CD were also tested, but these did not form stable complexes with the DNA and produced only a slight improvement in transfection level over DNA alone. The polycationic CDs neutralised DNA to form stable nanoparticulate complexes. The transfection efficiency of these CDs was dependent on the substituents present, with the most efficient having either an amino, pyridylamino or butylimidazole group at the 6-positions and unmodified 2- and 3-hydroxyls. One of the most effective vectors, heptakispyridylamino CD, produced a 4000-fold increase in transfection level over DNA alone. Levels were improved 10-fold by use of the endosomolytic agent, chloroquine. The transfection efficiency of the best of these systems in serum equals that of DOTAP in serum. Studies with 32P-labelled plasmid DNA indicate that the polycationic CDs are exceptional promoters of DNA cellular-uptake, the most efficient surpassing DOTAP. Uptake is dependent on proteoglycan-mediated binding to cells. The data imply that intracellular trafficking but not cellular uptake, may be the rate-limiting step in the transfection process. These initial results indicate that CDs are useful templates for further modification to produce molecular constructs capable of enhanced gene delivery.
- Cryan, Sally-Ann,Holohan, Ann,Donohue, Ruth,Darcy, Raphael,O'Driscoll, Caitriona M.
-
-
Read Online
- Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann-Pick type C disease-like HepG2 cells
-
Niemann-Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD). The aim of the present study was to synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi-Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD (DSL 5.6) as compared to TRITC-HP-β-CD was observed in NPC-like HepG2 cells. Further, the dissociation constant of peanut lectin with multi-Lac-β-CD (DSL5.6) was found to be extremely low (2.5 × 10-8 M). These results indicate that multi-Lac-β-CD (DSL5.6) diminished intracellular cholesterol levels in NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis.
- Motoyama, Keiichi,Nishiyama, Rena,Maeda, Yuki,Higashi, Taishi,Ishitsuka, Yoichi,Kondo, Yuki,Irie, Tetsumi,Era, Takumi,Arima, Hidetoshi
-
-
Read Online
- Method for synthesizing beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in water phase
-
The invention discloses a method for synthesizing a beta-hydroxy carbonyl compound by catalyzing asymmetric Aldol reaction in a water phase. The method comprises the following steps: in the water phase, catalyzing ketone and aldehyde with equal molar weig
- -
-
Paragraph 0032; 0035-0036
(2021/01/28)
-
- β-Cyclodextrin Covalent Organic Framework for Selective Molecular Adsorption
-
Covalent organic frameworks (COF) are complex functional systems constructed with atomic precision by linking well-defined building blocks through robust covalent bonds. β-cyclodextrin (β-CD) is a most employed supramolecule which bears a hydrophobic cavity guiding molecular specific recognitions. Building COF with asymmetric β-CD linkers is challenging and has never been reported. Here, β-CD COF is grown with heptakis(6-amino-6-deoxy)-β-CD and terephthalaldehyde in green solvents of water and ethanol at room temperature. The COF is characterized by powder X-ray diffraction, which matches well with the simulated crystal structure. Weaving β-CD into a framework through reticular chemistry allows the integration of a large amount of β-CD units (50 mol %), much higher than β-CD polymers. The β-CD COF has larger surface area, more uniform pore size, and higher thermal stability than the non-crystalline β-CD polymer produced by the same reagents. Finally, the β-CD COF holds abundant specific interaction sites enabling selective molecular adsorption.
- Wang, Ren-Qi,Wei, Xue-Bing,Feng, Yu-Qi
-
supporting information
p. 10979 - 10983
(2018/07/31)
-
- INHIBITION OF GALECTIN 3 BINDING TO THE AIRWAY EPITHELIAL SURFACE TO TREAT OR PREVENT SEPTIC SHOCK RESULTING FROM INFLUENZA AND SUBSEQUENT PNEUMOCOCCAL PNEUMONIA INFECTION
-
Galectin 3 inhibitors and methods for treating sepsis using the same are provided herein.
- -
-
-
- Self-assembly PEGylation retaining activity (SPRA) technology via a host-guest interaction surpassing conventional PEGylation methods of proteins
-
Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present "self-assembly PEGylation retaining activity" (SPRA) technology via a host-guest interaction between PEGylated β-cyclodextrin (PEG-β-CyD) and adamantane-appended (Ad) proteins. PEG-β-CyD formed stable complexes with Ad-insulin and Ad-lysozyme to yield SPRAinsulin and SPRA-lysozyme, respectively. Both SPRA-proteins showed high stability against heat and trypsin digest, comparable with that of covalently PEGylated protein equivalents. Importantly, the SPRA-lysozyme possessed ca. 100% lytic activity, whereas the activity of the covalently PEGylated lysozyme was ca. 23%. Additionally, SPRA-insulin provided a prolonged and peakless blood glucose profile when compared with insulin glargine. It also showed no loss of activity. In contrast, the covalently PEGylated insulin showed a negligible hypoglycemic effect. These findings indicate that SPRA technology has potential as a generic method, surpassing conventional PEGylation methods for proteins.
- Hirotsu, Tatsunori,Higashi, Taishi,Hashim, Irhan Ibrahim Abu,Misumi, Shogo,Wada, Koki,Motoyama, Keiichi,Arima, Hidetoshi
-
p. 368 - 376
(2017/02/15)
-
- Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
-
A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.
- Nag, Sananda,Duarte, Lisday,Bertrand, Emilie,Celton, Véronique,Castro, Micka?l,Choudhary, Veena,Guegan, Philippe,Feller, Jean-Fran?ois
-
supporting information
p. 6571 - 6579
(2015/03/13)
-
- Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers
-
A novel electronic nose system comprising functionalized β-cyclodextrin wrapped reduced graphene oxide (RGO) sensors with distinct ability of discrimination of a set of volatile organic compounds has been developed. Non-covalent modification of chemically functionalized cyclodextrin with RGO is carried out by using pyrene adamantane as a linker wherever necessary, in order to construct a supramolecular assembly. The chemical functionality on cyclodextrin is varied utilising the principle of selective chemical modification of cyclodextrin. In the present study, the combined benefits of the host-guest inclusion complex formation ability and tunable chemical functionality of cyclodextrin, as well as the high surface area and electrical conductivity of graphene, are utilized for the development of a set of highly selective quantum resistive chemical vapour sensors (QRS), which can be assembled in an electronic nose.
- Nag, Sananda,Duarte, Lisday,Bertrand, Emilie,Celton, Vronique,Castro, Mickal,Choudhary, Veena,Guegan, Philippe,Feller, Jean-Franois
-
supporting information
p. 6571 - 6579
(2015/05/20)
-
- Folate-appended β-cyclodextrin as a promising tumor targeting carrier for antitumor drugs in vitro and in vivo
-
A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c2-β-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c2-β-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (>106 M-1). Cellular uptake of DOX was increased by the addition of Fol-c2-β-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c2-β-CyD increased in vitro antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c2-β- CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c2-β-CyD could be useful as a promising antitumor drug carrier.
- Okamatsu, Ayaka,Motoyama, Keiichi,Onodera, Risako,Higashi, Taishi,Koshigoe, Takahiro,Shimada, Yasutaka,Hattori, Kenjiro,Takeuchi, Tomoko,Arima, Hidetoshi
-
p. 724 - 733
(2013/07/05)
-
- Design and evaluation of folate-appended α-, β-, and γ-Cyclodextrins having a caproic acid as a tumor selective antitumor drug carrier in vitro and in vivo
-
We reported that per-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c2-β-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c1-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c 1-β-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c1-α-CyD and Fol-c1-γ-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c 1-β-CyD, but not with Fol-c1-α-CyD or Fol-c1-γ-CyD in KB cells, a folate receptor-α-positive cell line. Also, Fol-c1-β-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c 1-β-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c1-β-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c1-β-CyD could be useful as a tumor-selective carrier for antitumor drugs.
- Okamatsu, Ayaka,Motoyama, Keiichi,Onodera, Risako,Higashi, Taishi,Koshigoe, Takahiro,Shimada, Yasutaka,Hattori, Kenjiro,Takeuchi, Tomoko,Arima, Hidetoshi
-
p. 4420 - 4428
(2014/01/06)
-
- Synthesis of poly(2-methyl-2-oxazoline) star polymers with a β-cyclodextrin core
-
Synthesis of star polymers with a-cyclodextrin (CD) core was undertaken using the arm-first, then the core-first strategy. Cationic ring opening polymerisation (CROP) of 2-methyl-2-oxazoline (MeOx) was first initiated by allyl bromide, and then quenched with heptakis(6-deoxy-6-amino)-CD in order to get a 7-arm star polymer. Then heptakis(6-deoxy-6-iodo-2,3-di-O-acetyl)-CD was synthesised in order to get an initiator for the CROP of MeOx. Initiation and propagation kinetic measurements were undertaken and the ratio kp/ki was found to be too high to provide a controlled polymerisation. Using iodine as co-initiator allowed a decrease of the kp/ki ratio that gave better control of the polymerisation. DOSY NMR and viscosity characterisations were undertaken, and both techniques lead to the demonstration of a lower hydrodynamic volume of the star polymers versus the linear counterparts, for compounds of the same molecular weight.
- Pereira, Guillaume,Huin, Ccile,Morariu, Simona,Bennevault-Celton, Vronique,Gugan, Philippe
-
p. 1145 - 1155
(2012/10/29)
-
- Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens
-
Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E2) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD-E2 conjugate was explored by cell reporter assays and confocal fluorescence microscopy. In simile with reported dendrimer-E2 conjugates, CD-E2 was found to be a stable, extranuclear receptor selective estrogen that penetrated into the cytoplasm.
- Kim, Hye-Yeong,Sohn, Johann,Wijewickrama, Gihani T.,Edirisinghe, Praneeth,Gherezghiher, Teshome,Hemachandra, Madhubani,Lu, Pei-Yi,Chandrasena, R. Esala,Molloy, Mary Ellen,Tonetti, Debra A.,Thatcher, Gregory R.J.
-
experimental part
p. 809 - 821
(2010/05/02)
-
- CYCLODEXTRIN DERIVATIVES AS POTENTIATORS FOR ANTIBIOTICS
-
The invention provides a new class of antibiotics that are derivatives of cyclodextrin, which is a cyclic molecule comprising D-glucose units. In addition, the invention provides a method for potentiating the activity of antibiotic to inhibit the growth o
- -
-
Page/Page column 60
(2009/06/27)
-
- Recognition of ionic guests by ionic β-cyclodextrin derivatives
-
Inclusion compounds of cationic, anionic, and neutral p-substituted derivatives of feri-butylbenzene complexed in β-cyclodextrin and its ionic 6-mono and 6-hepta derivatives were systematically investigated by isothermal titration calorimetry (ITC). All inclusion compounds showed 1:1 stoichiometry with binding constants ranging from 10 to 3 × 106 M -1. The binding free energies could be subdivided into apolar and electrostatic contributions. The electrostatic interactions could be quantitatively described by Coulomb's law by taking into account the degree of protonation of hosts and guests, the orientations of the guests within the hosts, and ion shielding as described by the Debye-Hueckel-Onsager theory. The orientations of the guests within the cyclodextrin cavities were determined by ROESY NMR spectroscopy.
- Wenz, Gerhard,Strassnig, Christian,Thiele, Carolin,Engelke, Annegret,Morgenstern, Bernd,Hegetschweiler, Kaspar
-
scheme or table
p. 7202 - 7211
(2009/08/14)
-
- Per(6-guanidino-6-deoxy)cyclodextrins: Synthesis, characterisation and binding behaviour toward selected small molecules and DNA
-
Per(6-guanidino-6-deoxy)-cyclodextrins 4a, 4b and 4c are novel derivatives, resulting from homogeneous introduction of the guanidino group at the primary side of α-, β- and γ-cyclodextrins. The products were obtained from the corresponding amino derivatives, as direct guanidinylation of the known bromo-cyclodextrins provided mixtures. The new compounds were fully characterized by NMR spectroscopy and other analytical methods, and their interaction with guest molecules was studied. Strong complexation with 4-nitrophenyl phosphate (NPP) disodium salt was observed (Kbinding ~5 × 104 M-1), whereas the non-phosphorylated substrate nitrobenzene (NB) formed a very weak complex. 2D ROESY spectra revealed cavity inclusion in both cases, however the orientation of NPP was opposite to that of NB, such that the phosphate group is oriented toward the primary side facing the guanidine groups. The strong affinity of 4 towards the phosphorylated guest suggested that interaction with DNA was possible. The new compounds were found to completely inhibit the migration of ultra pure calf thymus DNA during agarose gel electrophoresis, whereas no effects were observed with guanidine alone or with the plain cyclodextrins. Further, the condensation of DNA into nanoparticles in the presence of 4b was demonstrated by atomic force microscopy, confirming strong electrostatic interaction between the biopolymer and the multicationic products 4. The strong guanidine-phosphate interactions between 4 and DNA were therefore attributed to the clustering of the guanidine groups in the primary area of the cyclodextrin. Cavity effects could not be assessed. This journal is The Royal Society of Chemistry.
- Mourtzis, Nikolaos,Eliadou, Kyriaki,Aggelidou, Chrysie,Sophianopoulou, Vassiliki,Mavridis, Irene M.,Yannakopoulou, Konstantina
-
p. 125 - 131
(2008/03/14)
-
- β-Cyclodextrin derivatives that inhibit anthrax lethal toxin
-
Recently, we demonstrated that simultaneous blocking of bacterial growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using β-cyclodextrin as the starting molecule. Several β-cyclodextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment.
- Karginov, Vladimir A.,Yohannes, Adiamseged,Robinson, Tanisha M.,Fahmi, Nour Eddine,Alibek, Kenneth,Hecht, Sidney M.
-
-
- An efficient protocol for the reduction of azidocyclodextrins catalyzed by indium
-
In the presence of indium, the reduction of various substituted azidocyclodextrins to aminocyclodextrins proceeds in excellent yields.
- Reddy, L. Rajender,Reddy, M. Arjun,Bhanumathi,Rama Rao
-
p. 645 - 646
(2007/10/03)
-
- Amino acid derivatives of β-cyclodextrin
-
The syntheses of the heptaamino acid-substituted β-cyclodextrins per-6-[(phenylalanyl)amino]-β-cyclodextrin (6), per-6-cysteinyl-β-cyclodextrin (7), as well as the per-2,3-dimethyl-per-6-cysteinyl-β-cyclodextrin (12) are described. The amino acids were coupled to the primary face of the β-cyclodextrin torus using the backbone carboxylic acid functionality of phenylalanine and the side chain thiol group of cysteine. In the case of the heptacysteinyl derivatives, polyzwitterionic compounds were obtained and shown to be highly water soluble.
- Ashton, Peter R.,Koeniger, Rainer,Stoddart, J. Fraser,Alker, David,Harding, Valerie D.
-
p. 903 - 908
(2007/10/03)
-
- Synthesis of symmetrical cyclodextrin derivatives bearing multiple charges
-
Several water-soluble symmetrical cyclodextrin derivatives bearing positively charged or negatively charged groups were synthesized to examine the possibility of obtaining stable electrostatically linked heterodimers in water.The positively charged specie
- Guillo, Frederique,Hamelin, Bertrand,Jullien, Ludovic,Canceill, Josette,Lehn, Jean-Marie,et al.
-
p. 857 - 866
(2007/10/02)
-