53958-47-7

Usage

Uses

Used in Pharmaceutical Industry:
HEPTAKIS-6-AZIDO-6-DEOXY-BETA-CYCLODEXTRIN, 1:1 DMF COMPLEX, 95 is used as a reactant for the preparation of cyclodextrin amino acid derivatives. These derivatives have potential applications in drug delivery and enhancement of drug solubility, stability, and bioavailability.
Used in Chemical Synthesis:
In the field of chemical synthesis, HEPTAKIS-6-AZIDO-6-DEOXY-BETA-CYCLODEXTRIN, 1:1 DMF COMPLEX, 95 can be utilized as a versatile building block for the development of novel molecules with various applications, such as in supramolecular chemistry, materials science, and medicinal chemistry.
Used in Research and Development:
This complex molecule is also valuable in research and development, where it can be employed to study the interactions between cyclodextrin derivatives and various guest molecules, leading to a better understanding of molecular recognition and host-guest chemistry.

Upstream product

• 53784-83-1 heptakis(6-bromo-6-deoxy)-β-cyclodextrin 
• 30754-23-5 heptakis(6-deoxy-6-iodo)cyclomaltoheptaose 
• 155953-27-8 heptakis-(6-chloro-6-deoxy)-β-cyclodextrin 
• 7585-39-9 β‐cyclodextrin 

Downstream Products

• 30754-24-6 heptakis(6-amino-6-deoxy)-β-cyclodextrin 
• 1610587-75-1 C₁₃₃H₁₆₁N₂₁O₄₂ 

Relevant academic research and scientific papers

Temperature sensitive supramolecular self assembly of per-6-PEO-β-cyclodextrin and α,ω-di-(adamantylethyl)poly(N-isopropylacrylamide) in water

The host/guest interactions in water of a star polymer consisting of a β-cyclodextrin (β-CD) core bearing six poly(ethylene oxide) arms linked to the C6 positions of β-CD (β-CD-PEO7, Mn 5000 g mol-1) and α,ω-di-(adamantylethyl)poly(N-isopropylacrylamide) (Ad-PNIPAM-12K, Mn 12 000 g mol-1) were studied by 1D and 2D 1H and 13C NMR spectroscopy, isothermal calorimetry (ITC), and light scattering (LS). In cold water (T 7 and Ad-PNIPAM-12K undergo a reversible heat-induced phase transition at ～32°C, accompanied by a release of a fraction of the Ad-bound β-CD-PEO7 into bulk solution and the formation of aggregated Ad-PNIPAM-12K stabilized by a β-CD-PEO7 shell.

6-Hydroxymethyltriazolyl-6-deoxy-β-cyclodextrin: A highly water soluble and structurally well-defined β-cyclodextrin click cluster

The structural, physical, and biological properties of heptakis{6-(4- hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HTβCD) were investigated by a variety of methods, including NMR, UV/vis, circular dichroism spectroscopy, computer modeling, turbidity testing, Ka measurements, and the MTT assay. The experimental results suggest that HTβCD is structurally well-defined, highly water-soluble, and has low cytotoxicity. These advantages of HTβCD versus β-CD indicate that β-cyclodextrin click clusters may function both as host molecules and as potential, alternative excipients to β-CD.

Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin

To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (HT-β-CD(OMe)2 ), and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (ST-β-CD). The CCCs were prepared using copper(I)-catalyzed azide-alkyne cycloaddition from 6-azido-6-deoxy-β-CD and their water solubility, cytotoxicity, and drug-solubilizing effect were investigated. Water turbidity testing of the CCCs showed that the minimum water solubility of the CCCs is at least 20 times higher than that of β-CD. An MTT cell viability assay performed on HeLa cells demonstrated a low cytotoxicity of the CCCs compared with 2,6-dimethyl-β-cyclodextrin. HT-β-CD(OMe)2 and ST-β-CD did not demonstrate any cytotoxicity within the experimental concentration (～5 mM) like 2-hydroxypropyl-β-CD. A phase-solubility study of prednisolone with the CCCs suggested that CCCs showed increased solubility of prednisolone in the presence of increasing concentrations of the CCCs. The comparison between the conventional CD derivatives and CCCs on solubility, cytotoxicity, and binding property implies that CCCs are alternative cyclodextrin derivatives useful for overcoming the restrictions of conventional cyclodextrin chemistry.

6-Triazolyl-6-deoxy-β-cyclodextrin derivatives: synthesis, cellular toxicity, and phase-solubility study

Heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy} -β-cyclodextrin (HTβCD) and heptakis{6-(4-sulfonylmethyl-1H-[1,2,3] triazol-1-yl)-6-deoxy}-β-cyclodextrin (STβCD) were prepared using copper(I)-catalyzed azide-alkyne cycloaddition between 6-azido-6-deoxy-β-CD and one of two alkynes, propargyl alcohol, and sodium propargyl sulfonate, respectively. The structures of HTβCD and STβCD were characterized by NMR techniques. NMR interpretations and computer modeling suggested that the limited freedom of rotation of the triazole moieties keeps HTβCD and STβCD rigid and compact. Water solubility tests of HTβCD and STβCD showed that the minimum water solubility of HTβCD and STβCD is at least 20 times higher than that of β-CD. MTT assay showed that HTβCD and STβCD did not influence the cell viability under 1 mM. A phase-solubility study of prednisolone with the CD derivatives showed increased solubility of prednisolone in the presence of increasing concentrations of HTβCD and STβCD.

Facial Synthesis and Bioevaluation of Well‐Defined OEGylated Betulinic Acid‐Cyclodextrin Conjugates for Inhibition of Influenza Infection

Betulinic acid (BA) and its derivatives exhibit a variety of biological activities, especially their anti‐HIV‐1 activity, but generally have only modest inhibitory potency against influenza virus. The entry of influenza virus into host cells can be competitively inhibited by multivalent derivatives targeting hemagglutinin. In this study, a series of hexa‐, hepta‐ and octavalent BA derivatives based on α-, β-and γ-cyclodextrin scaffolds, respectively, with varying lengths of flexible oligo(ethylene glycol) linkers was designed and synthesized using a microwave‐assisted copper‐catalyzed 1,3‐di-polar cycloaddition reaction. The generated BA‐cyclodextrin conjugates were tested for their in vitro activity against influenza A/WSN/33 (H1N1) virus and cytotoxicity. Among the tested com-pounds, 58, 80 and 82 showed slight cytotoxicity to Madin‐Darby canine kidney cells with viabilities ranging from 64 to 68% at a high concentration of 100 μM. Four conjugates 51 and 69–71 showed significant inhibitory effects on influenza infection with half maximal inhibitory concentration val-ues of 5.20, 9.82, 7.48 and 7.59 μM, respectively. The structure‐activity relationships of multivalent BA‐cyclodextrin conjugates were discussed, highlighting that multivalent BA derivatives may be potential antiviral agents against influenza infection.

Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host-guest interaction between cyclodextrin and adamantane. We show that the host-guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.

The uncommon strong inhibition of α-glucosidase by multivalent glycoclusters based on cyclodextrin scaffolds

The homeostasis disruption of d-glucose causes diabetes, a dramatic chronic disease worldwide. Type 1 diabetes is a successfully treatable form, where blood d-glucose is regulated by insulin treatment. In contrast type 2 diabetes, the non-insulin dependent kind, is problematic. The control of the d-glucose blood level via intestinal α-d-glucosidase inactivation can be achieved by using competitive inhibitors, such as iminosugars (e.g. acarbose) or sulfonium sugar derivatives (e.g. salacinol). Recently, an unprecedented result showed that multivalent diamond nanoparticles grafted with unmodified sugars displayed α-glucosidase inhibition at low micromolar concentrations. Herein we describe the synthesis of multivalent glycoclusters using cyclodextrins (CDs) as scaffolds and an assessment of their role as inhibitors of α-d-glucosidase. The glycoclusters were efficiently obtained from per-azido α, β and γ-CD derivatives and propargyl glycosides using click-chemistry under microwave irradiation. The methodology was successfully applied to various protected and non-protected propargylated monosaccharides, including both O- and S-glycosides, giving clear evidence of its versatility. The targeted 6-per-glycosylated CDs were isolated in moderate to excellent yields (30-90%) by silica gel chromatography. The results showed inhibition of α-glucosidase from Saccharomyces cerevisiae with IC50 values in the 32-132 μM range, lower than that of acarbose (IC50 = ～250 μM), a well-known competitive inhibitor used in the clinical treatment of type 2 diabetes. Preliminary experiments suggest a mixed-type non-competitive inhibition mode for these new glycoclusters.

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.

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.

Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on “smart” particles

Overexpression of RhoC protein in breast cancer patients has been linked to increased cancer cell invasion, migration, and metastases. Suppressing RhoC expression in aggressive breast cancer cells using silencing RNA (siRNA) molecules is a viable strategy to inhibit the metastatic spread of breast cancer. In this report, we describe the synthesis of a series of asymmetric pH-sensitive, membrane-destabilizing polymers engineered to complex anti-RhoC siRNA molecules forming “smart” nanoparticles. Using β-CD as the particle core, polyethylene glycol (PEG) chains were conjugated to the primary face via non-cleavable bonds and amphiphilic polymers incorporating hydrophobic and cationic monomers were grafted to the secondary face via acid-labile linkages. We investigated the effect of PEG molecular weight (2 & 5 kDa) on transfection capacity and serum stability of the formed particles. We evaluated the efficacy of EPPT1 peptides presented on the free tips of the PEG brush to function as a targeting ligand against underglycosylated MUC1 (uMUC1) receptors overexpressed on the surface of metastatic breast cancer cells. Results show that “smart” nanoparticles successfully delivered anti-RhoC siRNA into the cytoplasm of aggressive SUM149 and MDA-MB-231 breast cancer cells, which resulted in a dose-dependent inhibition of cell migration and invasion. Further, EPPT1-targeted nanoparticles demonstrate a synergistic inhibition of cell migration and invasion imparted via RhoC knockdown and EPPT1-mediated signaling via the uMUC1 receptor.