86770-74-3Relevant articles and documents
Photo-responsive Bioactive Surfaces Based on Cucurbit[8]uril-Mediated Host–Guest Interactions of Arylazopyrazoles
Wiemann, Maike,Niebuhr, Rebecca,Juan, Alberto,Cavatorta, Emanuela,Ravoo, Bart Jan,Jonkheijm, Pascal
, p. 813 - 817 (2018)
A photoswitchable arylazopyrazole (AAP) derivative binds with cucurbit[8]uril (CB[8]) and methylviologen (MV2+) to form a 1:1:1 heteroternary host–guest complex with a binding constant of Ka=2×103 m?1. The excellent photoswitching properties of AAP are preserved in the inclusion complex. Irradiation with light of a wavelength of 365 and 520 nm leads to quantitative E- to Z- isomerization and vice versa, respectively. Formation of the Z-isomer leads to dissociation of the complex as evidenced using 1H NMR spectroscopy. AAP derivatives are then used to immobilize bioactive molecules and photorelease them on demand. When Arg-Gly-Asp-AAP (AAP–RGD) peptides are attached to surface bound CB[8]/MV2+ complexes, cells adhere and can be released upon irradiation. The heteroternary host–guest system offers highly reversible binding properties due to efficient photoswitching and these properties are attractive for designing smart surfaces.
Synthesis and pH-dependent self-assembly of semifluorinated calix[4]arenes
Martin, Oana M.,Mecozzi, Sandro
, p. 5539 - 5547 (2007)
A new series of highly fluorinated calix[4]arene-based amphiphilic molecules was designed and synthesized. Using the calix[4]arene scaffold, four perfluorinated hyper-hydrophobic groups and four water solubilizing chains were introduced in the same molecule and also segregated in space following the scaffold directionality. Upon solubilization in aqueous solutions, these amphiphilic molecules form microscopic fluorous domains that drive the formation of various self-assembly patterns. We found that the self-assembly of these semifluorinated calix[4]arenes is dependent on external stimuli, such as changes in the polarity of the solvent or pH. As a consequence, by changing the pH of?the solutions, it is possible to shift the aggregation pattern of these molecules, by a regular change either in the shape or in the size of the?initially formed ordered aggregates. These are examples of the variety of structures and possibilities in nano-engineering offered by fluorous-phase driven molecular recognition.
Supramolecular compound nano-carrier as well as preparation method and application thereof
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, (2021/08/14)
The invention discloses a supramolecular compound nano-carrier as well as a preparation method and application thereof, and relates to the technical field of polymer chemistry and biological detection engineering. According to the supramolecular compound nano-carrier disclosed by the invention, a two-dimensional nanosheet supramolecular structure system generated by self-assembly is driven by an anion induction effect, and a supramolecular compound nano-carrier is of a single-layer nanosheet supramolecular structure constructed by a highly-oriented one-dimensional nanorod. A hydrophobic perylene group part is used as a skeleton part for constructing the highly-oriented one-dimensional nanorod, and the charge density of a single-layer nanosheet can be regulated and controlled. The surface of the water-soluble multivalent hydrophilic part can be loaded with DNAzyme deoxyribozyme for specific detection of heavy metal ions through electrostatic interaction, and the water-soluble multivalent supramolecular compound nano sensor is constructed. Based on a fluorescence change mechanism caused by specific cutting of heavy metal ions, The fluorescence detection of the heavy metal ions in food and biological tissues is realized, and the detection effect of the heavy metal ions is greatly enhanced.
Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
Chen, Yuwen,Huang, Yulan,Jiao, Wei,Li, Fu,Li, Suiyan,Li, Wenhua,Lin, Yuan,Liu, Wanli,Ma, Yuling,Sheng, Yuwen,Suksamrarn, Apichart,Wang, Fei,Wang, Jing,Wei, Xiao,Wisanwattana, Wisanee,Wu, Wenbi,Zeng, Zhongqiu,Zhang, Guolin,Zhang, Jichao,Zhu, Qiyu
, (2022/01/03)
Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.
BIVALENT TARGETED CONJUGATES
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, (2020/05/28)
The invention provides conjugates that comprise a bivalent targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates, compositions comprising the bidentate targeting ligands and the conjugates, as well as methods for targeting therapeutic nucleic acids with the bidentate conjugates. The conjugates are useful to target therapeutic nucleic acids.
THERAPEUTIC METHODS
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, (2020/05/28)
The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
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, (2020/06/17)
The invention provides a PROTAC compound represented by formula I and used for targeted degradation of IDO1, and a pharmaceutically acceptable salt, a hydrate or a solvate thereof. In the formula I, Xrepresents -CH2 or -C = O, Y represents -CH2 or -C= O, and n is a natural number from 2 to 9. The PROTAC compound for targeted degradation of the IDO1 has efficient activity of targeted degradation of the IDO1 protein.
A Cleavable C2-Symmetric trans-Cyclooctene Enables Fast and Complete Bioorthogonal Disassembly of Molecular Probes
Carlson, Jonathan C. T.,Haider, Maximilian,Herrmann, Barbara,Klubnick, Jenna,Mikula, Hannes,Sohr, Barbara,Weissleder, Ralph,Wilkovitsch, Martin
supporting information, p. 19132 - 19141 (2020/11/13)
Bioorthogonal chemistry is bridging the divide between static chemical connectivity and the dynamic physiologic regulation of molecular state, enabling in situ transformations that drive multiple technologies. In spite of maturing mechanistic understanding and new bioorthogonal bond-cleavage reactions, the broader goal of molecular ON/OFF control has been limited by the inability of existing systems to achieve both fast (i.e., seconds to minutes, not hours) and complete (i.e., >99%) cleavage. To attain the stringent performance characteristics needed for high fidelity molecular inactivation, we have designed and synthesized a new C2-symmetric trans-cyclooctene linker (C2TCO) that exhibits excellent biological stability and can be rapidly and completely cleaved with functionalized alkyl-, aryl-, and H-tetrazines, irrespective of click orientation. By incorporation of C2TCO into fluorescent molecular probes, we demonstrate highly efficient extracellular and intracellular bioorthogonal disassembly via omnidirectional tetrazine-triggered cleavage.
A MedChem toolbox for cereblon-directed PROTACs
Steinebach, Christian,Sosi?, Izidor,Lindner, Stefanie,Bricelj, Ale?a,Kohl, Franziska,Ng, Yuen Lam Dora,Monschke, Marius,Wagner, Karl G.,Kr?nke, Jan,Gütschow, Michael
, p. 1037 - 1041 (2019/06/27)
A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We also highlight different opportunities for the expansion of the medicinal chemists' PROTAC toolbox towards heterobifunctional molecules, e.g. with biotin, fluorescent, hydrophobic and peptide tags.
Set of Highly Stable Amine- and Carboxylate-Terminated Dendronized Au Nanoparticles with Dense Coating and Nontoxic Mixed-Dendronized Form
Saha Ray, Arunendra,Ghann, William E.,Tsoi, Phoebe S.,Szychowski, Brian,Dockery, Lance T.,Pak, Yewon J.,Li, Wenjing,Kane, Maureen A.,Swaan, Peter,Daniel, Marie-Christine
, p. 3391 - 3403 (2019/03/07)
The synthesis of a novel poly(propyleneimine) (PPI) dendron in gram scale as well as its use in the formation of a highly stable, dendronized gold nanoparticle (AuNP)-based drug delivery platform is described herein. The AuNP-based platform is composed of three complementary parts: (i) a 15 nm AuNP core, (ii) a heterofunctional thioctic acid-terminated tetraethylene glycol spacer, and (iii) a third-generation PPI dendron with a unique protonation profile and diverse end-group functionalization that allows for further derivatization. The prepared dendronized AuNPs are able to withstand several rounds of lyophilization cycles with no sign of aggregation, are stable in phosphate-buffered saline and Hanks' buffer as well as in serum, and are resistant to degradation by glutathione exchange reactions. This nanocarrier platform displays a dense coating, with >1400 dendrons/AuNPs, which will enable very high payload. Furthermore, while amine-terminated AuNPs expectedly showed cytotoxicity against the MCF-7 breast cancer cell line from a NP concentration of 1 nM, the mixed monolayer AuNPs (coated with 40/60 amine/carboxylate dendrons) interestingly did not exhibit any sign of toxicity at concentrations as high as 15 nM, similar to the carboxylate-terminated AuNPs. The described dendronized AuNPs address the current practical need for a stable NP-based drug delivery platform which is scalable and easily conjugable, has long-term stability in solution, and can be conveniently formulated as a powder and redispersed in desired buffer or serum.
