153086-78-3Relevant articles and documents
Shell cross-linked nanoparticles designed to target angiogenic blood vessels via αvβ3 receptor-ligand interactions
Pan, Dipanjan,Turner, Jeffrey L.,Wooley, Karen L.
, p. 7109 - 7115 (2004)
The design, synthesis, and characterization of a novel polymeric nanostructured material bearing surface-attached integrin antagonists are demonstrated. The covalent coupling of a complex and biologically active small molecule to a well-defined nanostructured material combines the elegance of synthetic organic chemistry with the state-of-the-art polymer chemistry. This unique material offers potential in targeting to tumor neovasculature and delivery of diagnostic and therapeutic agents.
A cholesterol-based tether for creating photopatterned lipid membrane arrays on both a silica and gold surface
Han, Xiaojun,Achalkumar, Ammathnadu S.,Bushby, Richard J.,Evans, Stephen D.
, p. 6363 - 6370 (2009)
We report a new cholesterolbased self-assembled monolayer (SAM) for use in attaching lipid membranes to both gold and silica surfaces that can be patterned by deep UV (254 nm) photolysis. It allows essentially equivalent patterned supported bilayers to be created both on gold for impedance studies and on silica for fluorescence studies. On either surface an amine-functionalised SAM is reacted with an N-hydroxysuccinimidylcarbonyl-functionalised E03-cholesteryl derivative. The formation of the aminefunctionalised SAM and its reaction with the E03-cholesteryl derivative were followed by contact-angle measurements, ellipsometry and X-ray pho-toelectron spectroscopy. The resultant layer of cholesterol tethers was patterned by deep UV photolysis, which regenerates the original SiO2 surface in exposed regions on a silica substrate and oxidises thiol groups on a gold substrate. This patterned surface containing hydrophilic SiO2 (or -OH groups) and hydrophobic cholesterol tether regions can be converted to a surface patterned with supported lipid bi- and monolayers (respectively) by immersing in a solution of small unilamellar vesicles of egg yolk phosphatidycholine. The formation of the lipid bi- and monolayer regions on the silica surface was evidenced by fluorescence microscopy. Crucially the bilayer regions remain fully fluid yielding lipid mobilities comparable to those found in physisorbed bilayers. Furthermore charged fluorescent lipids are shown to migrate in an applied field thus providing a platform for the studying the electrophoresis (potentially) for a wide range of charged membrane components, such as membrane proteins. The formation of the patterned lipid membrane on the gold surface was confirmed by electrochemical impedance measurements.
Evaluation of the synthesis of sialic Acid-PAMAM glycodendrimers without the use of sugar protecting Groups, and the Anti-HIV-1 properties of these compounds
Clayton, Russell,Hardman, Janee,Labranche, Celia C.,McReynolds, Katherine D.
, p. 2186 - 2197 (2011)
A study was undertaken to evaluate the feasibility of synthesizing six sialic acid-PAMAM glycodendrimers using unprotected sialic acid in as few as 1-4 steps using two different reaction pathways, and to assess the sulfated derivatives for anti-HIV activity. The syntheses were accomplished through either the direct attachment of the sialic acid carboxyl group to amine-terminated PAMAM (a divergent-like approach) using BOP coupling, or by first reacting sialic acid with a polar bifunctional spacer molecule, attaching the sugar-linker to carboxy-terminated PAMAM (a convergent-like approach), and again using BOP-mediated coupling reactions. It was hypothesized that the latter approach would be the most successful method, as any steric congestion between the sialic acid and the PAMAM would be minimized using an intervening polar linker. However, the divergent-like synthesis proved to be the superior method, resulting in 11.4%, 14%, and 28% of the fully substituted generations 0, 1, and 2 sialic acid-PAMAM conjugates, respectively, as compared to 6.4% of only the generation ?0.5 sialic acid-linker-PAMAM conjugate for the convergent-like method. Upon sulfation of the four glycodendrimers, binding capabilities to the recombinant HIV protein, gp120, were assessed using an ELISA assay. Compounds that showed promising binding characteristics were then further assessed for inhibition of HIV-1 infection using a well-characterized luciferase reporter gene neutralization assay. The generation 2 sulfated sialic acid-PAMAM glycodendrimer, sulfo-6, bearing 16 sialic acids with 11 sulfate groups incorporated at 4.03% sulfur content by weight, was found to inhibit all four HIV-1 strains tested in the low micromolar range.
A Specific and Covalent JNK-1 Ligand Selected from an Encoded Self-Assembling Chemical Library
Zimmermann, Gunther,Rieder, Ulrike,Bajic, Davor,Vanetti, Sara,Chaikuad, Apirat,Knapp, Stefan,Scheuermann, J?rg,Mattarella, Martin,Neri, Dario
, p. 8152 - 8155 (2017)
We describe the construction of a DNA-encoded chemical library comprising 148 135 members, generated through the self-assembly of two sub-libraries, containing 265 and 559 members, respectively. The library was designed to contain building blocks potentially capable of forming covalent interactions with target proteins. Selections performed with JNK1, a kinase containing a conserved cysteine residue close to the ATP binding site, revealed the preferential enrichment of a 2-phenoxynicotinic acid moiety (building block A82) and a 4-(3,4-difluorophenyl)-4-oxobut-2-enoic acid moiety (building block B272). When the two compounds were joined by a short PEG linker, the resulting bidentate binder (A82-L-B272) was able to covalently modify JNK1 in the presence of a large molar excess of glutathione (0.5 mm), used to simulate intracellular reducing conditions. By contrast, derivatives of the individual building blocks were not able to covalently modify JNK1 in the same experimental conditions. The A82-L-B272 ligand was selective over related kinases (BTK and GAK), which also contain targetable cysteine residues in the vicinity of the active site.
Anion interaction with ferrocene-functionalised cyclic and open-chain polyaza and aza-oxa cycloalkanes
Beer, Paul D.,Cadman, James,Lloris, Jose Manuel,Martinez-Manez, Ramoen,Soto, Juan,Pardo, Teresa,Dolores Marcos
, p. 1805 - 1812 (2000)
A family of ferrocene-functionalised receptors of different topologies have been used as receptors for anions. The compounds have been designed to contain both amine nitrogen and ether oxygen atoms and comprises from monoaza to pentaaza derivatives both open-chain (L1, L2, L3) or cyclic (L4, L5) and having from one to five ferrocenyl groups. Solution studies directed to determine the protonation constants of L1, L2 and L3 have been carried out in water (0.1 mol dm3 KNO3, 25 °C) and those of L4 and L5 in 1,4-dioxane-water (70:30 v/v, 0.1 mol dm-3 KNO3, 25 °C). The protonation behaviour of the receptors can be explained taking into account electrostatic considerations. Speciation studies in the presence of phosphate have been carried out in water for L', L2 and L3 and in dioxane-water for L4 and L5. Speciation studies have also been performed in the presence of ATP with L1, L2 and L3 in water. Selectivity of a mixture of receptors against a certain anion is discussed in terms of ternary diagrams. The shift of the redox potential of the ferrocenyl groups as a function of the pH has been studied. The difference between the oxidation potentials at basic and acidic pH has been determined experimentally and is compared with that theoretically predicted using an electrostatic model previously reported. The electrochemical shift in the presence of ATP and phosphate has been measured in water for L1, L2 and L3 and in the presence of phosphate and sulfate in 1,4-dioxane-water for L4 and L5 as a function of the pH. The electrochemical response found against those anions is quite poor with maximum cathodic shifts off. 30tO mV. The electrochemical response induced by HSO4 and H2PO4- has also been studied in acetonitrile solutions where a large cathodic shift for H2PO4- up to ca. 200 mV was found. The Royal Society of Chemistry 2000.
Dynamic multivalent interaction of phenylboronic acid functionalized dendrimers with vesicles
Otremba, Tobias,Ravoo, Bart Jan
, p. 4972 - 4978 (2017)
Over the past decade cyclodextrin vesicles were established as a versatile model for biological membranes since they can be easily modified with functional groups due to the spontaneous formation of host-guest complexes. In this article we report the inte
Functionalization of diameter-sorted semiconductive SWCNTs with photosensitizing porphyrins: Syntheses and photoinduced electron transfer
Das, Sushanta K.,Subbaiyan, Navaneetha K.,D'Souza, Francis,Sandanayaka, Atula S. D.,Zandler, Melvin E.,Ito, Osamu
, p. 11388 - 11398,11 (2012)
Covalent functionalization of diameter sorted SWCNTs with porphyrins (MP), and photochemistry to establish nanotube diameter-dependent charge separation efficiencies are reported. The MP-SWCNT(n,m) [M=2 H or Zn, and (n,m)=(7,6) or (6,5)] nanohybrids are c
Synthesis of C-4 and C-7 triazole analogs of zanamivir as multivalent sialic acid containing scaffolds
Lu, Yan,Gervay-Hague, Jacquelyn
, p. 1636 - 1650 (2007)
The relative reactivities of C-4 and C-7 azides derived from zanamivir were compared in cycloaddition reactions with a panel of alkynes. All of the reactions proceeded efficiently with no observable differences between primary and secondary azides. Signif
Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme
Rublack, Nico,Mueller, Sabine
, p. 1906 - 1913 (2014)
Over the past 20 years, the generation of functional RNAs by in vitro selection has become a standard technique. Apart from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated.
Optimised approach to albumin-drug conjugates using monobromomaleimide-C-2 linkers
Wall, Archie,Nicholls, Karl,Caspersen, Mikael B.,Skrivergaard, Stig,Howard, Kenneth A.,Karu, Kersti,Chudasama, Vijay,Baker, James R.
, p. 7870 - 7873 (2019)
Conjugation of therapeutics to human serum albumin (HSA) using bromomaleimides represents a promising platform for half-life extension. We show here that the Cys-34 crevice substantially reduces the rate of serum stabilising maleimide hydrolysis in these
A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells
Glaffig, Markus,Stergiou, Natascha,Hartmann, Sebastian,Schmitt, Edgar,Kunz, Horst
, p. 25 - 29 (2018)
A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose-receptor-positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non-mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di- and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose-coupled vaccine and the non-mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells.
COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CALCIUM ION HOMEOSTASIS
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Page/Page column 71, (2021/08/20)
The present disclosure relates to compounds that are capable of modulating calcium ion homeostasis and treating disorders related thereto. The disclosure further relates to methods of making the aforementioned compounds.
A Color-Shifting Near-Infrared Fluorescent Aptamer–Fluorophore Module for Live-Cell RNA Imaging
Zhang, Jingye,Wang, Lu,J?schke, Andres,Sunbul, Murat
supporting information, p. 21441 - 21448 (2021/08/23)
Fluorescent light-up RNA aptamers (FLAPs) have become promising tools for visualizing RNAs in living cells. Specific binding of FLAPs to their non-fluorescent cognate ligands results in a dramatic fluorescence increase, thereby allowing RNA imaging. Here, we present a color-shifting aptamer-fluorophore system, where the free dye is cyan fluorescent and the aptamer-dye complex is near-infrared (NIR) fluorescent. Unlike other reported FLAPs, this system enables ratiometric RNA imaging. To design the color-shifting system, we synthesized a series of environmentally sensitive benzopyrylium-coumarin hybrid fluorophores which exist in equilibrium between a cyan fluorescent spirocyclic form and a NIR fluorescent zwitterionic form. As an RNA tag, we evolved a 38-nucleotide aptamer that selectively binds the zwitterionic forms with nanomolar affinity. We used this system as a light-up RNA marker to image mRNAs in the NIR region and demonstrated its utility in ratiometric analysis of target RNAs expressed at different levels in single cells.
