- Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies
-
23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe 26c were performed in B16F10 cells, and the results suggested that probe 26c was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent.
- Yao, Hong,Wei, Guoxiang,Liu, Yanpeng,Yao, Hequan,Zhu, Zheying,Ye, Wencai,Wu, Xiaoming,Xu, Jinyi,Xu, Shengtao
-
-
Read Online
- Controlling cellular distribution of drugs with permeability modifying moieties
-
Phenotypic screening provides compounds with very limited target cellular localization data. In order to select the most appropriate target identification methods, determining if a compound acts at the cell-surface or intracellularly can be very valuable. In addition, controlling cell-permeability of targeted therapeutics such as antibody-drug conjugates (ADCs) and targeted nanoparticle formulations can reduce toxicity from extracellular release of drug in undesired tissues or direct activity in bystander cells. By incorporating highly polar, anionic moieties via short polyethylene glycol linkers into compounds with known intracellular, and cell-surface targets, we have been able to correlate the cellular activity of compounds with their subcellular site of action. For compounds with nuclear (Brd, PARP) or cytosolic (dasatinib, NAMPT) targets, addition of the permeability modifying group (small sulfonic acid, polycarboxylic acid, or a polysulfonated fluorescent dye) results in near complete loss of biological activity in cell-based assays. For cell-surface targets (H3, 5HT1A, β2AR) significant activity was maintained for all conjugates, but the results were more nuanced in that the modifiers impacted binding/activity of the resulting conjugates. Taken together, these results demonstrate that small anionic compounds can be used to control cell-permeability independent of on-target activity and should find utility in guiding target deconvolution studies and controlling drug distribution of targeted therapeutics.
- Richardson, Paul L.,Marin, Violeta L.,Koeniger, Stormy L.,Baranczak, Aleksandra,Wilsbacher, Julie L.,Kovar, Peter J.,Bacon-Trusk, Patricia E.,Cheng, Min,Hopkins, Todd A.,Haman, Sandra T.,Vasudevan, Anil
-
-
Read Online
- Cell-Surface Receptor-Ligand Interaction Analysis with Homogeneous Time-Resolved FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI-Anchored Receptors
-
Ligand-binding assays are the linchpin of drug discovery and medicinal chemistry. Cell-surface receptors and their ligands have traditionally been characterized by radioligand-binding assays, which have low temporal and spatial resolution and entail safety risks. Here, we report a powerful alternative (GlycoFRET), where terbium-labeled fluorescent reporters are irreversibly attached to receptors by metabolic glycan engineering. For the first time, we show time-resolved fluorescence resonance energy transfer between receptor glycans and fluorescently labeled ligands. We describe GlycoFRET for a GPI-anchored receptor, a G-protein-coupled receptor, and a heterodimeric cytokine receptor in living cells with excellent sensitivity and high signal-to-background ratios. In contrast to previously described methods, GlycoFRET does not require genetic engineering or antibodies to label receptors. Given that all cell-surface receptors are glycosylated, we expect that GlycoFRET can be generalized with applications in chemical biology and biotechnology, such as target engagement, receptor pharmacology, and high-throughput screening.
- Stockmann, Henning,Todorovic, Viktor,Richardson, Paul L.,Marin, Violeta,Scott, Victoria,Gerstein, Clare,Lake, Marc,Wang, Leyu,Sadhukhan, Ramkrishna,Vasudevan, Anil
-
-
Read Online
- HaloTag protein-mediated site-specific conjugation of bioluminescent proteins to quantum dots
-
On the dot: A genetically engineered haloalkane dehalogenase was used to conjugate Renilla luciferase to quantum dots (see picture). The quantum dots can emit light through bioluminescence resonance energy transfer (BRET). This specific conjugation occurs upon simple mixing under mild conditions, and may be applied for specific in vivo labeling of proteins with quantum dots for imaging. (Figure Presented).
- Zhang, Yan,So, Min-Kyung,Loening, Andreas M.,Yao, Hequan,Gambhir, Sanjiv S.,Rao, Jianghong
-
-
Read Online
- Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma
-
Traditional EZH2 inhibitors are developed to suppress the enzymatic methylation activity, and they may have therapeutic limitations due to the nonenzymatic functions of EZH2 in cancer development. Here, we report proteolysis-target chimera (PROTAC)-based EZH2 degraders to target the whole EZH2 in lymphoma. Two series of EZH2 degraders were designed and synthesized to hijack E3 ligase systems containing either von Hippel-Lindau (VHL) or cereblon (CRBN), and some VHL-based compounds were able to mediate EZH2 degradation. Two best degraders, YM181 and YM281, induced robust cell viability inhibition in diffuse large B-cell lymphoma (DLBCL) and other subtypes of lymphomas, outperforming a clinically used EZH2 inhibitor EPZ6438 (tazemetostat) that was only effective against DLBCL. The EZH2 degraders displayed promising antitumor activities in lymphoma xenografts and patient-derived primary lymphoma cells. Our study demonstrates that EZH2 degraders have better therapeutic activity than EZH2 inhibitors, which may provide a potential anticancer strategy to treat lymphoma.
- Tu, Yalin,Sun, Yameng,Qiao, Shuang,Luo, Yao,Liu, Panpan,Jiang, Zhong-Xing,Hu, Yumin,Wang, Zifeng,Huang, Peng,Wen, Shijun
-
p. 10167 - 10184
(2021/07/26)
-
- DEGRADATION OF BRUTON'S TYROSINE KINASE (BTK) BY CONJUGATION OF BTK INIDBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE
-
Disclosed herein are novel bifunctional compounds formed by conjugating BTK inhibitor moieties with E3 ligase Ligand moieties, which function to recruit targeted proteins to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof.
- -
-
-
- Polyethylene glycol coupling medicine as well as preparation method and application thereof
-
The invention relates to the technical field of medicines, relates to a polyethylene glycol coupled drug as well as a preparation method and an application thereof, and in particular relates to a polyethylene glycol coupled drug as shown in a formula I or pharmaceutically acceptable salt thereof. The invention also relates to a preparation method of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof, and the application of the polyethylene glycol coupled drug or the pharmaceutically acceptable salt thereof in preparation of drugs.
- -
-
-
- Method for preparing semaglutide side chain by liquid phase method
-
The invention discloses a method for preparing a semaglutide side chain. The preparation method comprises the following steps: protecting amino of an initial raw material 2-(2-aminoethoxy) ethanol byusing R1; then carrying out nucleophilic substitution reaction with alpha halogenated ester to prolong a carbon chain; preparing an aliphatic chain with two protected ends by a one-pot method; removing a protecting group at one end of each aliphatic chain and condensing to obtain a compound 7; removing the R1 protecting group to obtain a compound 8, performing condensation reaction on the compound8 and fluorenylmethoxycarbonyl-L-glutamic acid 1-tert-butyl ester to obtain a compound 10, removing the fluorenylmethoxycarbonyl, performing amidation condensation reaction on the compound 10 and 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 13, and removing the R2 protecting group to obtain a target product chain 1. Compared with solid-phase synthesis, the method disclosed by theinvention is lower in cost and wider in selection of protecting groups, and has industrial production and application prospects.
- -
-
Paragraph 0077-0079; 072
(2020/07/02)
-
- Method for synthesizing semaglutide side chain in liquid-phase convergent manner
-
The invention discloses a method for synthesizing a semaglutide side chain 1 in a liquid-phase convergent manner. The method comprises the steps: protecting amino of a raw material 2-(2-aminoethoxy)ethanol by using R1; then carrying out nucleophilic substitution reaction with ethyl bromoacetate; carrying out ester hydrolysis in one pot to obtain a compound 4; protecting carboxyl of the compound 4with R2; removing R1 to obtain a compound 6; carrying out condensation reaction on the compound 6 and fluorenylmethoxycarbonyl-L-glutamic acid 1-tert-butyl ester, to obtain a compound 8; removing R2 of the compound 8, and carrying out a coupling reaction with the compound 6 to obtain a compound 10; removing Fmoc of the compound 10, carrying out an amidation condensation coupling reaction with 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 13; and removing R2 of the compound 13 to obtain the product 1. The method has the advantages of effective and controllable synthesis process,low cost and high yield, and can be suitable for large-scale production.
- -
-
Paragraph 0078-0080
(2020/06/30)
-
- Convergent liquid-phase synthesis method of semaglutide side chain
-
A synthesis method of a semaglutide side chain 1 comprises the following steps: protecting a terminal amino group of a raw material diglycolamine 2 by using R1, then carrying out nucleophilic substitution reaction with alpha halogenated ester, and carrying out ester hydrolysis in one pot to obtain a compound 4; protecting the free carboxyl of the compound 4 by R2, and removing the R1 protected group to obtain a compound 6; carrying out condensation reaction on a compound 7 and the compound 6 to obtain a compound 8; removing fluorenylmethoxycarbonyl of the compound 8, carrying out an amidationcondensation coupling reaction on the compound 8 and 18-(tert-butoxy)-18-oxooctadecanoic acid to obtain a compound 11; removing the R2 protected group of the compound 11, carrying out a condensation coupling reaction on the compound 11 and the compound 6 to obtain a compound 13; and removing the R2 protected group of the compound 13 to obtain the chain 1. A convergent synthesis method is used to reduce the reaction cost and shorten the reaction time, the synthesis process is effective and controllable, the cost is low, the yield is high, and the method is suitable for large-scale production.
- -
-
Paragraph 0071; 0093-0097
(2020/07/08)
-
- Liquid-phase synthesis method of semaglutide side chain
-
The invention discloses a liquid-phase synthesis method of a semaglutide side chain. The liquid-phase synthesis method comprises the following steps: taking diglycolamine and an X radical to react, soas to protect an amino terminal of the diglycolamine through the X radical; then realizing hydroxyl protection through the amino terminal and a reaction carboxyl terminal of benzyl bromoacetate, so as to remove benzyl and the X radical; after coupling two products without the radical, removing the X radical; then coupling with an Fmoc-glutamic acid and removing Fmoc; finally coupling with 18-(tert-butoxy)-18oxooctadecanoic acid and then removing the benzyl to obtain the semaglutide side chain. The method disclosed by the invention has the advantages that a synthesis method process is feasible, controllable, low in cost and high in yield; the synthesis method is applicable to large-scale production; the semaglutide side chain is finally prepared and can be directly assembled to a semaglutide main chain in a liquid phase after being modified into OSu ester.
- -
-
Paragraph 0057; 0063; 0064
(2019/08/03)
-
- COMPOUNDS AND METHODS FOR OPTICAL SENSING OF ELECTRICAL ACTIVITY IN BIOLOGICAL SYSTEMS
-
Disclosed are tethered chromophore compositions comprising a membrane-spanning tether. The compounds can include covalently tethered fluorophore-quencher combinations useful for measuring action potentials and other fast electrical events in cells and tissues.
- -
-
Paragraph 0097
(2019/08/20)
-
- Enzyme-mediated dynamic combinatorial chemistry allows out-of-equilibrium template-directed synthesis of macrocyclic oligosaccharides
-
We show that the outcome of enzymatic reactions can be manipulated and controlled by using artificial template molecules to direct the self-assembly of specific products in an enzyme-mediated dynamic system. Specifically, we utilize a glycosyltransferase to generate a complex dynamic mixture of interconverting linear and macrocyclic α-1,4-d-glucans (cyclodextrins). We find that the native cyclodextrins (α, β and γ) are formed out-of-equilibrium as part of a kinetically trapped subsystem, that surprisingly operates transiently like a Dynamic Combinatorial Library (DCL) under thermodynamic control. By addition of different templates, we can promote the synthesis of each of the native cyclodextrins with 89-99% selectivity, or alternatively, we can amplify the synthesis of unusual large-ring cyclodextrins (δ and ?) with 9 and 10 glucose units per macrocycle. In the absence of templates, the transient DCL lasts less than a day, and cyclodextrins convert rapidly to short maltooligosaccharides. Templates stabilize the kinetically trapped subsystem enabling robust selective synthesis of cyclodextrins, as demonstrated by the high-yielding sequential interconversion of cyclodextrins in a single reaction vessel. Our results show that given the right balance between thermodynamic and kinetic control, templates can direct out-of-equilibrium self-assembly, and be used to manipulate enzymatic transformations to favor specific and/or alternative products to those selected in Nature.
- Larsen, Dennis,Beeren, Sophie R.
-
p. 9981 - 9987
(2019/11/14)
-
- EXENATIDE MODIFIER AND USE THEREOF
-
Disclosed are an exenatide modifier for connecting the exenatide to a fatty chain with a carboxy in the terminus thereof by means of a hydrophilic connecting arm, and a use thereof in preparing drugs serving as a GLP-1 receptor agonist; a use in preparing drugs for preventing and/or treating diseases and/or symptoms associated with a low GLP-1 receptor activity; a use in preparing drugs for diseases and/or symptoms associated with glycometabolism; a use in preparing drugs for diabetes; a use in preparing drugs for fatty liver disease, and a use in preparing drugs for losing weight.
- -
-
Paragraph 0240
(2018/05/24)
-
- Anticancer intermediate based on PKI-587 and polyethylene glycol coupled anticancer drug, and preparation methods and application thereof
-
The invention provides an anticancer intermediate based on PKI-587 and a polyethylene glycol coupled anticancer drug, and preparation methods and application thereof, belonging to the field of treatment of cancers. The anticancer intermediate has a general structural formula as described in the specification, and at least one AC in the general structural formula is the anticancer drug PKI-587. Thepolyethylene glycol coupled anticancer drug has a general structural formula as described in the specification. The above two drugs can realize combined medication of the targeting anticancer drug PKI-587 and a plurality of other anticancer drugs, so toxic response caused by mutual influence and pharmacokinetics of a plurality of other anticancer drugs can be prevented during individual administration of the anticancer drugs, multidrug resistance of cancers is overcome, and synergistic effect is exerted; and the two drugs can be used for preparing anticancer drugs with targeting effect and have critical clinical value and wide market prospects.
- -
-
-
- With synergistic anti-cancer activity of the intermediate drug and polyethylene glycol coupled synergistic anti-cancer drug, and its preparation method and application (by machine translation)
-
The present invention provides synergistic anti-cancer activity of the intermediate drug and polyethylene glycol coupled synergistic anti-cancer drug, and its preparation method and application, which belongs to the field of cancer treatment. The has a synergistic anti-cancer activity of the general structural formula of intermediate drug The polyethylene glycol coupled synergistic anti-cancer drug the general structural formula of This two categories of drugs can realize a plurality of anticancer drug between the combination, to avoid a separate taking a plurality of anti-cancer drugs owing to the mutual influence between the pharmacokinetics and caused toxic reaction, and helps overcome the cancer of the multi-drug resistance, has synergistic effects, can be used for the preparation of anticancer drugs, has significant clinical value and broad market prospect. (by machine translation)
- -
-
-
- Oligomer and related compd. [...] -
-
The invention relates to (among other things) oligomer-calcimimetic conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over previously administered compounds.
- -
-
Paragraph 0228
(2016/11/07)
-
- Cyclic Peptidomimetic Compounds as Immunomodulators
-
The present invention relates to cyclic peptidomimetic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them.
- -
-
Paragraph 0150; 0151
(2015/03/16)
-
- CYCLIC PEPTIDOMIMETIC COMPOUNDS AS IMMUNOMODULATORS
-
The present invention relates to cyclic peptidomimetic compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The invention also relates to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them.
- -
-
Page/Page column 26; 27
(2015/03/28)
-
- Selective synthesis of a [3]rotaxane consisting of size-complementary components and its stepwise deslippage
-
An α-cyclodextrin-based size-complementary [3]rotaxane with an alkylene axle was selectively synthesized in one pot via an end-capping reaction with 2-bromophenyl isocyanate in water. Thermal degradation of the [3]rotaxane product yielded not only the ori
- Akae, Yosuke,Okamura, Hisashi,Koyama, Yasuhito,Arai, Takayuki,Takata, Toshikazu
-
supporting information; experimental part
p. 2226 - 2229
(2012/06/30)
-
- Red-fluorescent argininamide-type NPY Y1 receptor antagonists as pharmacological tools
-
Fluorescently labelled NPY Y1 receptor (Y1R) ligands were synthesized by connecting pyrylium and cyanine dyes with the argininamide-type Y1R antagonist core structure by linkers, covering a wide variety in length and chemical nature, attached to the guanidine group. The most promising fluorescent probes had Y1R affinities (radioligand binding) and antagonistic activities (calcium assay) in the one- to two-digit nanomolar range. These compounds turned out to be stable under assay conditions and to be appropriate for the detection of Y1Rs by confocal microscopy in live cells. To improve the signal-to-noise ratio by shifting the emission into the near infrared, a new benzothiazolium-type fluorescent cyanine dye (UR-DE99) was synthesized and attached to the parent antagonist via a carbamoyl linker yielding UR-MK131, a highly potent fluorescent Y1R probe, which was also successfully applied in flow cytometry.
- Keller, Max,Erdmann, Daniela,Pop, Nathalie,Pluym, Nikola,Teng, Shangjun,Bernhardt, Günther,Buschauer, Armin
-
experimental part
p. 2859 - 2878
(2011/06/22)
-
- Coordination-assembly for quantitative construction of bis-branched molecular shuttles
-
The development and utilization of a new way to build molecular devices is of importance. To build a novel topology of interlocked molecular systems with a controllable mechanical motion, an axle-like compound comprising azobenzene and alkoxy isophthalate
- Zhu, Liangliang,Lu, Meiqun,Qu, Dahui,Wang, Qiaochun,Tian, He
-
scheme or table
p. 4226 - 4233
(2011/07/29)
-
- Altered product specificity of a cyclodextrin glycosyltransferase by molecular imprinting with cyclomaltododecaose
-
Cyclodextrin glycosyltransferases (CGTases), members of glycoside hydrolase family 13, catalyze the conversion of amylose to cyclodextrins (CDs), circular α-(1,4)-linked glucopyranose oligosaccharides of different ring sizes. The CD containing 12 α-D-gluc
- Kaulpiboon, Jarunee,Pongsawasdi, Piamsook,Zimmermann, Wolfgang
-
experimental part
p. 480 - 485
(2011/12/02)
-
- A novel heterotrifunctional peptide-based cross-linking reagent for facile access to bioconjugates. Applications to peptide fluorescent labelling and immobilisation
-
A convenient, versatile and straightforward synthesis of a novel heterotrifunctional peptide-based linker molecule is described. This generic bio-labelling reagent contains an amine-reactive N-hydroxysuccinimidyl carbamate moiety, an aldehyde/ketone-reactive aminooxy group and a thiol group with a propensity to form urea, oxime and thioether linkages respectively. The full chemical orthogonality between the free aminooxy and thiol functionalities was demonstrated through the preparation of a fluorescent reagent suitable for the selective staining of a carboxaldehyde-modified surface by means of oxime ligation. The absence of reactivity of these two functions toward the nucleophile-sensitive active carbamate was obtained by using temporary aminooxy- and thiol-protecting groups removable under mild conditions. The utility of the linker molecule to cross-link three different molecular partners has been illustrated by the preparation of fluorescent tripod-functionalised surfaces which may be useful in developing new peptide microarrays and related immunosensors.
- Clavé, Guillaume,Boutal, Hervé,Hoang, Antoine,Perraut, Fran?ois,Volland, Hervé,Renard, Pierre-Yves,Romieu, Anthony
-
supporting information; experimental part
p. 3065 - 3078
(2009/02/03)
-
- Methods of synthesizing and using derivatives of [2-(2-aminoethoxy)ethoxy] acetic acid
-
A synthetic reaction to produce [2-(2-aminoethoxy)ethoxy] acetic acid (AEEA) derivatives. This synthetic reaction does not require isolation and purification of intermediates. The AEEA derivatives can be used to synthesize high load polystyrene-polyethylene glycol-like resins having excellent swelling characteristics.
- -
-
-
- Isolation of Paenibacillus illinoisensis that produces cyclodextrin glucanotransferase resistant to organic solvents.
-
A bacterium that secreted cyclodextrin glucanotransferase (CGTase) in a medium overlaid with n-hexane was isolated and identified as Paenibacillus illinoisensis strain ST-12 K. The CGTase of the strain was purified from the culture supernatant. The molecular mass was 70 kDa. The enzyme was stable at pH 6 to 10 and active at pH 5.0 to 8.0. The optimum temperature at pH 7.0 was 65 degrees C in the presence of 5 mM CaCl2. The enzyme produced mainly beta-cyclodextrin. The total yield of alpha-, beta-, and gamma- cyclodextrins was increased 1.4-fold by the addition of ethanol. In particular, the yield of beta-cyclodextrins in the presence of 10% (vol/vol) ethanol was 1.6-fold that without ethanol. The CGTase was stable and active in the presence of large amounts of various organic solvents.
- Doukyu, Noriyuki,Kuwahara, Hirokazu,Aono, Rikizo
-
p. 334 - 340
(2007/10/03)
-
- Chemical synthesis of cyclodextrins by using intramolecular glycosylation
-
An efficient synthesis of cyclodextrins (CDs) by using the intramolecular glycosylation is demonstrated. α-CD, an α(1→4)linked hexaglucoside, was prepared via a block condensation of three maltose units. A modified key maltose intermediate as a precursor to both glycosyl donor and acceptor components was prepared in 6 steps starting from maltose. All the glycosylation for chain elongation and cyclization of saccharides was carried out after tethering the donor to the acceptor by the phthaloyl bridge to give the desired saccharides in good yields with complete α-selectivity. δ-CD composed of 9 glucose units was synthesized by the same manner from three maltotriose units.
- Wakao, Masahiro,Fukase, Koichi,Kusumoto, Shoichi
-
p. 8182 - 8190
(2007/10/03)
-
- Homogenous Enzymatic Synthesis Using a Thermo-Responsive Water-Soluble Polymer Support
-
Several enzymes immobilized on thermoresponsive polyacrylamide polymers are nearly as active as their soluble forms, and can be recovered for reuse after gentle heating and precipitation. Carbohydrates attached to these polymers have been used for enzymatic glycoslation, and the products have been isolated by thermal precipitation followed by release from the polymer, thus greatly simplifying product purification in water.
- Huang, Xuefei,Witte, Krista L.,Bergbreiter, David E.,Wong, Chi-Huey
-
p. 675 - 681
(2007/10/03)
-
- Rotaxane-encapsulation enhances the stability of an azo dye, in solution and when bonded to cellulose
-
A cyclodextrin coat dramatically enhances the stability of an azo dye towards reductive bleaching, oxidative bleaching, and photo-bleaching as is demonstrated by the rotaxane 1. This compound is obtained as single isomer in high yield from the amine-substituted dye and trichlorotriazine in water in the presence of the cyclodextrin.
- Craig, Michael R.,Hutchings, Michael G.,Claridge, Tim D. W.,Anderson, Harry L.
-
p. 1071 - 1074
(2007/10/03)
-
- Suitability and limitations of methods for characterisation of activity of malto-oligosaccharide-forming amylases
-
The suitability and limitations of essential methods and reference substrates used for characterisation of activity of amylolytic enzymes is investigated. Saccharogenic, chromogenic and chromatographic methods are included. The results are discussed in relation to the measurement of reaction rates, determination of action mode and product specificity and the impact on identification and nomenclature of malto-oligosaccharide-forming amylases. An accurate determination of reaction rates using the saccharogenic methods strongly depends on the degree of polymerisation (DP) of the standards used and the hydrolysis products formed by the amylase. Particularly the use of glucose as standard can lead to overestimates due to the differences in the reducing potential of glucose and malto-oligosaccharides. The reliability of the chromogenic methods for determination of action mode depends on the DP of the substrate and the specificity of the amylase. For a characterisation of the starch hydrolysis products and the variation in the DP during hydrolysis, high performance anion-exchange chromatography with pulsed amperometric detection provided a fast and reliable method. A literature survey revealed varying and inconsistent use of nomenclature of malto-oligosaccharide forming amylases. Therefore a systematic approach identifying three main classes of activity is suggested using not only the mode of action and the DP of the major product but also the stage of hydrolysis at which this product is formed. (C) 2000 Elsevier Science Ltd.
- Duedahl-Olesen, Lene,Haastrup Pedersen, Lars,Lambertsen Larsen, Kim
-
p. 109 - 119
(2007/10/03)
-
- Catalysis of ester aminolysis by cyclodextrins. The reaction of alkylamines with p-nitrophenyl alkanoates
-
The effects of four cyclodextrins (α-CD, β-CD, hydroxypropyl-β-CD, and γ-CD) on the aminolysis of p-nitrophenyl alkanoates (acetate to heptanoate) by primary amines (n-propyl to n-octyl, isobutyl, isopentyl, cyclopentyl, cyclohexyl, benzyl) in aqueous solution have been investigated. Rate constants for amine attack on the free and CD-bound esters (k(N) and k(cN)) have ratios (k(cN)/k(N)) varying from 0.08 (retardation) to 180 (catalysis). For the kinetically equivalent process of free ester reacting with CD-bound amine (k(Nc)), the ratios k(Nc)/k(N) vary from 0.2 to 28. Either way, there is evidence of catalysis in some cases and retardation in others. Changes in reactivity parameters with structure indicate more than one mode of transition state binding to the CDs. Short esters react with short alkylamines by attack of free amine on the ester bound by its aryl group, but for longer amines, free ester reacts with CD-bound amine. Reaction of long esters with long amines, which is catalyzed by β-CD and γ-CD, involves inclusion of the alkylamino group and possibly the ester acyl group. The larger cavity of γ-CD may allow the inclusion of the ester aryl group, as well as the alkylamino group, in the transition state. Reaction between an ester bound to the CD by its acyl group and free amine appears not to be important.
- Gadosy,Boyd,Tee
-
p. 6879 - 6889
(2007/10/03)
-
- Influence of cyclodextrins on the fluorescence of some short and long chain linked flexible bisbenzenes in aqueous solution
-
The UV absorption, induced circular dichroism (icd) spectra, steady state and time resolved fluorescence emission of the flexible bisbenzenes 1-4 were obtained in aqueous solution and in presence of α-, β-, and γ-cyclodextrin (CD). Bisbenzenes 1 and 2 in an aqueous environment exhibit a dual emission which is differently affected by the CDs. The long-wavelength emission is quenched by α- and β-CD and enhanced by γ-CD. This is due to the formation of inclusion complexes between the CDs and 1 (2) in the ground state, in agreement with the modifications of the UV spectrum and the appearance of icd signals. On the basis of these effects and of the influence of the CDs on the 1 and 2 lifetimes, the dual emission of these bisbenzenes is attributed to a set of different ground-state conformations.
- Bortolus, Pietro,Monti, Sandra,Smoluch, Miroslawa,Bouas-Laurent, Henri,Desvergne, Jean-Pierre
-
p. 1165 - 1171
(2007/10/03)
-
- Quantitative estimation of the bitter taste intensity of oxyphenonium bromide reduced by cyclodextrins from electromotive force measurements
-
The bitter taste of oxyphenonium bromide, an antiacetylcholine drug, is suppressed by cyclodextrins. The extent of the suppression can be predicted from the electromotive force measurements with an oxyphenonium bromide- selective electrode. The relationship between the bitter taste intensity and the electromotive force holds true, regardless of the kind and concentration of natural and modified cyclodextrins. This result is explicable on the basis of the observation that both the bitter taste and the electric potential are determined by the concentration of free oxyphenonium bromide. Some implications and limitations of the present approach are discussed.
- Funasaki, Noriaki,Kawaguchi, Ryusaku,Ishikawa, Seiji,Hada, Sakae,Neya, Saburo,Katsu, Takashi
-
p. 1733 - 1736
(2007/10/03)
-
- NMR Detection of Simultaneous Formation of [2]- and [3]Pseudorotaxanes in Aqueous Solution between α-Cyclodextrin and Linear Aliphatic α,ω-Amino acids, an α,ω-Diamine and an α,ω-Diacid of Similar Length, and Comparison with the Solid-State Structures
-
The interactions of 11-aminoundecanoic acid (1), 12-aminododecanoic acid (2), 1,12-diaminododecane (3), and 1,13-tridecanoic diacid (4) with α-cyclodextrin (αCD) were studied in aqueous solution by NMR spectroscopy. The association modes were established with titration and continuous variation plots, variable temperature NMR spectra, and dipolar interactions as recorded in 2D ROESY spectra. The studies were carried out at pH 7.3 and 13.6. These long, linear bifunctional molecules were found to form simultaneously [2]- and [3]pseudorotaxanes with αCD in the aqueous solution. At the higher pH the 1:1 adducts were present at concentrations higher than at the neutral pH. The longer guests formed complexes enriched in the 2:1 constituent at both pH values. There were clear indications that the [2]pseudorotaxanes are present in two isomeric forms. The presence of isomers also in the [3]pseudorotaxanes was not ruled out. Various exchange rate regimes were observed; clearly in neutral solutions the formation of the 1:1 complexes was fast in the NMR time scale, whereas the threading of a second αCD ring was a slower process. In the solid state, the adduct of αCD/2 had the structure of a [3]pseudorotaxane, in accordance with previously solved crystal structures of αCD/3 and βCD/4. The species in solution, in contrast with those present in the solid state, are therefore of varying nature, and thus the frequently and conveniently assumed 1:1 stoichiometry in similar systems is an oversimplification of the real situation.
- Eliadou, Kyriaki,Yannakopoulou, Konstantina,Rontoyianni, Aliki,Mavridis, Irene M.
-
p. 6217 - 6226
(2007/10/03)
-
- Retardation of acetal hydrolysis by cyclodextrins and its use in probing cyclodextrin-guest binding
-
Hydrolysis of benzaldehyde dimethyl acetal 1 in aqueous acid is slowed down greatly by cyclodextrins (SDs): α-CD, β-CD, hp-β-CD (hydroxypropyl-β-cyclodextrin) and γ-CD. The variations of the observed first-order rate constants (Kobs) with [CD] exhibit saturation behaviour consistent with 1:1 binding between 1 and the CDs. In the case of β-CD and hp-β-CD, the binding is relatively strong and the CD-bound acetal is unreactive. In contrast, binding of the acetal by α-CD and γ-CD is much weaker, but only with α-CD does the CD-bound form show significant reactivity. The four CD-mediated reaction, have been evaluated as probe reactions for determining dissociation constants of {CD-'guest'} complexes. In this approach, added guests attenuate the retarding effect of CD-substrate binding and cause an increase in the rate of acetal hydrolysis. The method works well for alipharic alcohols and ketones binding to β-CD and hp-β-CD, but it is less successful with α-CD because of the shallow dependence of kobs on [α-CD] in the probe action. With γ-CD, the approach is not applicable at all, because added guests cause a further reduction in the rate of acetal hydrolysis, not an increase. Various implications of these findings are discussed.
- Tee, Oswald S.,Fedortchenko, Alexei A.,Soo, Patrick Lim
-
p. 123 - 128
(2007/10/03)
-
- Kinetics of the self-assembly of α-cyclodextrin [2]pseudorotaxanes with 1,12-bis(4-(α-alkyl-α-methylmethanol)pyridinium)dodecane dications in aqueous solution
-
The kinetics and thermodynamics of the self-assembly of a series of [2]pseudorotaxanes comprised of α-cyclodextrin (α-CD) and racemic 1,12- bis(4-(α-alkyl-α-methylmethanol)pyridinium)dodecane dications (L(CH2)12L2+) in aqueous solutions have been investigated using 1H NMR spectroscopy. The mechanism of assembly involves inclusion of the α-methyl- α-alkylmethanol substituent groups (-C(CH3)(OH)R, where R = Me, Et, Pr, Bu, allyl, and 4-butenyl) by α-CD, followed by a rate-determining passage of the cyclodextrin over the pyridinium group onto the dodecamethylene chain. Dicationic threads containing end groups with R = Ph or i-Pr or where L = 4- (α,α-diethylmethanol)-pyridinium did not form α-cyclodextrin pseudorotaxanes, even after prolonged heating. The trends in the rate and activation parameters may be related to the size, shape, and hydrophobicity of the alkyl substituents and are compared with several other systems from the literature. An increase in the length and hydrophobicity of the alkyl group increases the strength of end group inclusion and decreases the rate of threading. In addition, the presence of unsaturation in the alkyl substituent (allyl vs propyl and 4-butenyl vs butyl) results in an increase in the threading rate constant.
- Smith, A. Catherine,Macartney, Donal H.
-
p. 9243 - 9251
(2007/10/03)
-
- Kinetics of the self-assembly of α-cyclodextrin [2]pseudorotaxanes with polymethylene threads bearing quaternary ammonium and phosphonium end groups
-
The kinetics and mechanism of the formation and dissociation of a series of [2]pseudorotaxanes, comprised of α-cyclodextrin (α-CD) as the cyclic component and the ([Me3N(CH2)(n)NMe3]2+ (n = 8-12), [Me2/sub
- Lyon, Angela P.,Banton, Nicola J.,Macartney, Donal H.
-
p. 843 - 850
(2007/10/03)
-
- Induced circular dichroism and UV-VIS absorption spectroscopy of cyclodextrin inclusion complexes: Structural elucidation of supramolecular azi-adamantane
-
The first induced circular dichroism (ICD) analyses of diazirineγyciodextrin inclusion complexes are reported. The stoichiometries and association constants of the guestηost complexes with α-, β-, and γ- cyclodextrin were determined. In addition, with the α-cyclodextrin complex, UV-vis spectroscopy of water-ethanol solutions showed remarkable fine structure, probably indicating that the diazirine experiences a nonpolar microenvironment. These analytical methods provide details about the architecture and nature of these supramolecular carbene precursors.
- Krois, Daniel,Brinker, Udo H.
-
p. 11627 - 11632
(2007/10/03)
-
- Inclusion effects of cyclomaltohexa- and heptaose (α- and β-cyclodextrins) on the acidities of several phenol derivatives
-
By means of spectrophotometry, equilibrium constants for the formation of 1:1 inclusion complexes of cyclomaltohexaose (α-cyclodextrin, α-CD) or cyclomaltoheptaose (β-CD) in aqueous solutions have been evaluated for neutral and anionic species of 3-cyanophenol, 4-cyanophenol, 3-nitrophenol, 4-nitrophenol, 4-bromophenol, and 4-methoxyphenol. Using the equilibrium constants of the neutral and anionic species, pK(a) values have been determined for the phenols bound to the α- and β-CD cavities. These phenols, which are accommodated in the α-CD cavity, have been found to be stronger acids than the free, uncomplexed ones, except for 4-methoxyphenol. On the other hand, 4-cyanophenol, 3-nitrophenol, and 4-methoxyphenol bound to the β-CD cavity are weaker acids than the uncomplexed ones, although,3-cyanophenol, 3-nitrophenol, and 3-bromophenol bound to β-CD show the same trend as those bound to α-CD. The different influences of α- and β-CDs on the pK(a) values are likely due to the difference in the magnitudes of the induced dipole moments of the guest caused by α- and β-CDs; depending on the magnitude of the induced dipole moment, the inclusion complexes are stabilized through the dipole-dipole interaction between the host and guest.
- Hamai, Sanyo,Satoh, Noriko
-
p. 229 - 237
(2007/10/03)
-
- Solid state polycondensation within cyclodextrin channels leading to watersoluble polyamide rotaxanes
-
α,ω-Aminocarboxylic acids form microcrystalline inclusion compounds with α-cyclodextrin. In these inclusion compounds cyclodextrins build up channel structures, in which the α,ω-aminocarboxylic acids can be polycondensed at 200-240°C. As the resulting pol
- Wenz, Gerhard,Steinbrunn, Marc Boris,Landfester, Katharina
-
p. 15575 - 15592
(2007/10/03)
-
- Thermodynamic and nuclear magnetic resonance study of the reactions of α- and β-cyclodextrin with acids, aliphatic amines, and cyclic alcohols
-
Titration calorimetry was used to determine equilibrium constants and standard molar enthalpy, Gibbs energy, and entropy changes for the reactions of a series of acids, amines, and cyclic alcohols with α- and β-cyclodextrin. The results have been examined in terms of structural features in the ligands such as the number of alkyl groups, the charge number, the presence of a double bond, branching, and the presence of methyl and methoxy groups. The values of thermodynamic quantities, in particular the standard molar Gibbs energy, correlate well with the structural features in the ligands. These structural correlations can be used for the estimation of thermodynamic quantities for related reactions. Enthalpy-entropy compensation is evident when the individual classes of substances studied herein are considered, but does not hold when these various classes of ligands are considered collectively. The NMR results indicate that the mode of accommodation of the acids and amines in the α-cyclodextrin cavity is very similar, but that the 1-methyl groups in 1-methylhexylamine and in 1-methylheptylamine and the N-methyl group in N-methylhexylamine lie outside the α-cyclodextrin cavity. This latter finding is consistent with the calorimetric results. Many of the thermodynamic and NMR results can be qualitatively understood in terms of van der Waals forces and hydrophobic effects.
- Rekharsky, Mikhail V.,Mayhew, Martin P.,Goldberg, Robert N.,Ross, Philip D.,Yamashoji, Yuko,Inoue, Yoshihisa
-
-
- Inclusion Complexes of Alcohols with α-Cyclodextrin
-
Calorimetric studies of the inclusion complexes of straight and branched alcohols and of diols with alpha-cyclodextrin (α-CD) have been carried out in water solvent.The data suggest that straight and branched chain alcohols enter the cavity of α-CD alkyl
- Spencer, J. N.,DeGarmo, Jarusha,Paul, I. M.,He, Qing,Ke, Xiaoming,et al.
-
p. 601 - 610
(2007/10/02)
-
- Dynamic aspects in host-guest interactions. Part 4. Kinetic and 1H NMR evidence for multi-step directional binding in the molecular recognition of some 2-naphthylazophenol guests with α-cyclodextrin
-
Detailed solution kinetic and equilibria data in aqueous solution are presented for the molecular recognition by α-cyclodextrin (α-CDx) of structurally different types of 2-naphthylazophenol guest. 1H NMR equilibrium titrations and stopped-flow
- Yoshida, Noboru
-
p. 2249 - 2256
(2007/10/03)
-
- Capillary Electrophoresis as a Method for Determining Binding Constants: Application to the Binding of Cyclodextrins and Nitrophenolates
-
For analytes involved in dynamic aquilibrium processes, capillary electrophoresis is a powerful method of determining binding constants.Equilibrium constants from capillary electrophoresis for the binding of nitrophenolates to α-cyclodextrin show good agreement with literature values obtained using calorimetric and spectroscopic methods, confirming capillary electrophoresis as a viable method.We show that it is imperative to make viscosity corrections, to study the full binding range, and to use an algorithm which calculates the concentration of free cyclodextrin rather than the total cyclodextrin concentration.Binding constants for analytes in a complex mixture can be determined simultaneously.The methods have been applied to 2-, 3-, and 4-nitrophenolates with native and derivatized α- and β-cyclodextrins, and results provide insight into the binding process.Data analysis methods for capillary electrophoresis are also successfully applied to liquid chromatography with the use of the same selector as mobile phase additive.
- Penn, Sharron G.,Bergstroem, Edmund T.,Knights, Ian,Liu, Gaoyuan,Ruddick, Andrew,Goodall, David M.
-
p. 3875 - 3880
(2007/10/02)
-
- Synthesis of a Cyclodextrin Heterodimer Having α- and β-Cyclodextrin Units and Its Cooperative and Site-Specific Binding
-
A cyclodextrin heterodimer, which has α- and β-cyclodextrin units as two different receptor sites, was prepared.It showed cooperative and site-specific binding to isoamyl p-dimethylaminobenzoate with the alkyl group included in the β-cyclodextrin cavity while dimethylaminobenzene moiety partially included in the α-cyclodextrin cavity.This binding mode was substantiated by the fact that the TICT emission of this guest is greatly enhanced by the cyclodextrin heterodimer.
- Wang, Yong,Ueno, Akihiko,Toda, Fujio
-
p. 167 - 170
(2007/10/02)
-
- Spectroscopic Studies on Exchange Properties in Through-Ring Cyclodextrin Complexes of Carbazole-Viologen Linked Compounds: Effects of Spacer Chain Length
-
Analysis of 1H NMR spectra (400 MHz) revealed a novel mode of interaction between cyclodextrin (CD) and carbazole-viologen linked compounds (CACnV), where the spacer chain was consisted of n methylene units (n = 4, 6, 8, 10, and 12).In the case of α-CD, the complexed species lived long enough to afford distinct proton signals, when the spacer chain was relatively long (n >/= 8).As to CAC12V, the equilibrium constant for the 1:1 complex was 4.9 * 104 M-1 at 30 deg C and coalescence temperatures for the proton signals exceeded 100 deg C.Clear NOEs were observedto prove strong interaction between the protons in the CD cavity and the spacer methylene groups of CAC12V.The spacer was concluded to be encased in the cavity of α-CD.In the case of β-CD, essentially the same "through-ring CD complex" was formed.The line shape analysis indicated that the free energies of activation at 70 deg C for complexation and decomplexation were 11.6 and 17.2 kcal/mol, respectively.Activation parameters for the α-CD complexes were evaluated by the rate of disappearance of intramolecular charge-transfer absorption (420 nm) on the addition of α-CD.The free energy of activation for decomplexation was found to exceed 22 kcal/mol in the α-CD complexes for CACnV (n = 8, 10, and 12).The viologen moiety of CACnV was concluded to be the site of entrance for forming "through-ring CD compex", and the large activation energies were ascribed to dehydration of viologen units to go through the CD cavity.
- Yonemura, Hiroaki,Kasahara, Motohiro,Saito, Hide,Nakamura, Hiroshi,Matsuo, Taku
-
p. 5765 - 5770
(2007/10/02)
-
- Solvent Effects on Chemical Processes. 2. Binding Constants of Methyl Orange with α-Cyclodextrin in Binary Aqueous-Organic Solvents
-
The standard free energy change for complex formation is written as a sum of effects from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect)
- Connors, Kenneth A.,Mulski, Michael J.,Andrea Paulson
-
p. 1794 - 1798
(2007/10/02)
-
- Photochemistry of Benzophenone-Cyclodextrin Inclusion Complexes
-
The photochemistry of benzophenone aqueous solutions in the presence of cyclodextrins (CDx) has been studied by stationary and pulsed techniques.Quenching of the phosphorescence is the consequence of hydrogen abstraction following the inclusion in the cyclodextrin cavity of the triplet benzophenone.The H-abstraction process has close analogies with the same reaction in micelles.Radical pair decay is controlled by the dimensions of the CDx cavity: intersystem crossing prevails in the presence of β-CDx, radical excit in the presence of α- and γ-CDx.The fate of the escaped radical also depends on the cavity dimensions, as revealed by the photoreduction quantum yields.
- Monti, Sandra,Flamigni, Lucia,Martelli, Alessandro,Bortolus, Pietro
-
p. 4447 - 4451
(2007/10/02)
-
- Contrasting Behaviors in the Cleavage of Aryl Alkanoates by α- and β-Cyclodextrins in Basic Aqueous Solution
-
The kinetics of ester cleavage of 4-carboxy-2-nitrophenyl alkanoates (C2, C4, C6, C7, C8) in aqueous base containing α- or β-cyclodextrin (α- or β-CD) indicate that for the three longer esters there are processes involving two CD molecules which are quite distinct: with α-CD a 2:1 binding leads to inhibition; with β-CD a second-order process provides catalysis.
- Tee, Oswald S.,Du, Xian-xian
-
p. 1837 - 1839
(2007/10/02)
-