- Photo-responsive Bioactive Surfaces Based on Cucurbit[8]uril-Mediated Host–Guest Interactions of Arylazopyrazoles
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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.
- Wiemann, Maike,Niebuhr, Rebecca,Juan, Alberto,Cavatorta, Emanuela,Ravoo, Bart Jan,Jonkheijm, Pascal
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Read Online
- Synthesis and pH-dependent self-assembly of semifluorinated calix[4]arenes
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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.
- Martin, Oana M.,Mecozzi, Sandro
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Read Online
- Supramolecular compound nano-carrier as well as preparation method and application thereof
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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.
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- Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
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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.
- 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
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- A Cleavable C2-Symmetric trans-Cyclooctene Enables Fast and Complete Bioorthogonal Disassembly of Molecular Probes
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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.
- Carlson, Jonathan C. T.,Haider, Maximilian,Herrmann, Barbara,Klubnick, Jenna,Mikula, Hannes,Sohr, Barbara,Weissleder, Ralph,Wilkovitsch, Martin
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supporting information
p. 19132 - 19141
(2020/11/13)
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- BIVALENT TARGETED CONJUGATES
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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.
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- THERAPEUTIC METHODS
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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.
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- PROTAC compound for targeted degradation of IDO1, and preparation method and application thereof
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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.
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- Set of Highly Stable Amine- and Carboxylate-Terminated Dendronized Au Nanoparticles with Dense Coating and Nontoxic Mixed-Dendronized Form
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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.
- 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
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p. 3391 - 3403
(2019/03/07)
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- GALNAC DERIVATIVES
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Modified oligonucleotides comprising a GalNAc moiety of the present disclosure along with methods of making and use, e.g., against HBV are disclosed.
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- A MedChem toolbox for cereblon-directed PROTACs
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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.
- 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
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p. 1037 - 1041
(2019/06/27)
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- Y-TYPE DISCRETE POLYETHYLENE GLYCOL DERIVATIVE AND PREPARATION METHOD THEREOF
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The present invention discloses a Y-type discrete polyethylene glycol derivative and a preparation method thereof, which has the advantages of determined molecular weights and the number of chain segments, and can avoid the defect of heterogeneity of a PEG derivative, meanwhile the preparation method has simple steps, mild conditions, without need for strictly anhydrous environment or performing protection and deprotection steps. In addition, the Y-type discrete polyethylene glycol derivative of the present invention may increase the water solubility of the discrete polyethylene glycol, and solve the problem of insufficient water solubility of the discrete polyethylene glycol-modified insoluble drug caused by an increase of the loading capacity.
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- Ligand-Phospholipid Conjugation: A Versatile Strategy for Developing Long-Acting Ligands That Bind to Membrane Proteins by Restricting the Subcellular Localization of the Ligand
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We hypothesized that if drug localization can be restricted to a particular subcellular domain where their target proteins reside, the drugs could bind to their target proteins without being metabolized and/or excreted, which would significantly extend the half-life of the corresponding drug-target complex. Thus, we designed ligand-phospholipid conjugates in which the ligand is conjugated with a phospholipid through a polyethylene glycol linker to restrict the subcellular localization of the ligand in the vicinity of the lipid bilayer. Here, we present the design, synthesis, pharmacological activity, and binding mode analysis of ligand-phospholipid conjugates with muscarinic acetylcholine receptors as the target proteins. These results demonstrate that ligand-phospholipid conjugation can be a versatile strategy for developing long-acting ligands that bind to membrane proteins in drug discovery.
- Kawamura, Shuhei,Ito, Yoshihiko,Hirokawa, Takatsugu,Hikiyama, Eriko,Yamada, Shizuo,Shuto, Satoshi
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supporting information
p. 4020 - 4029
(2018/05/07)
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- LUMINESCENT BIOMOLECULAR COMPLEX AND USE THEREOF
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The technology relates to biomolecular complex having an antibody-binding protein; a polypeptide linker capable of receiving a luminescence-activating unit; and a luminescence- activating unit. Also disclosed is the use of the biomolecular complex to detect biological target entities.
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- Hydrophilic and Cell-Penetrable Pyrrolidinyl Peptide Nucleic Acid via Post-synthetic Modification with Hydrophilic Side Chains
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Peptide nucleic acid (PNA) is a nucleic acid mimic in which the deoxyribose-phosphate was replaced by a peptide-like backbone. The absence of negative charge in the PNA backbone leads to several unique behaviors including a stronger binding and salt independency of the PNA-DNA duplex stability. However, PNA possesses poor aqueous solubility and cannot directly penetrate cell membranes. These are major obstacles that limit in vivo applications of PNA. In previous strategies, the PNA can be conjugated to macromolecular carriers or modified with positively charged side chains such as guanidinium groups to improve the aqueous solubility and cell permeability. In general, a preformed modified PNA monomer was required. In this study, a new approach for post-synthetic modification of PNA backbone with one or more hydrophilic groups was proposed. The PNA used in this study was the conformationally constrained pyrrolidinyl PNA with prolyl-2-aminocyclopentanecarboxylic acid dipeptide backbone (acpcPNA) that shows several advantages over the conventional PNA. The aldehyde modifiers carrying different linkers (alkylene and oligo(ethylene glycol)) and end groups (-OH, -NH2, and guanidinium) were synthesized and attached to the backbone of modified acpcPNA by reductive alkylation. The hybrids between the modified acpcPNAs and DNA exhibited comparable or superior thermal stability with base-pairing specificity similar to those of unmodified acpcPNA. Moreover, the modified apcPNAs also showed the improvement of aqueous solubility (10-20 folds compared to unmodified PNA) and readily penetrate cell membranes without requiring any special delivery agents. This study not only demonstrates the practicality of the proposed post-synthetic modification approach for PNA modification, which could be readily applied to other systems, but also opens up opportunities for using pyrrolidinyl PNA in various applications such as intracellular RNA sensing, specific gene detection, and antisense and antigene therapy.
- Pansuwan, Haruthai,Ditmangklo, Boonsong,Vilaivan, Chotima,Jiangchareon, Banphot,Pan-In, Porntip,Wanichwecharungruang, Supason,Palaga, Tanapat,Nuanyai, Thanesuan,Suparpprom, Chaturong,Vilaivan, Tirayut
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p. 2284 - 2292
(2017/09/26)
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- NANOPARTICLES FOR DIAGNOSIS AND DRUG DELIVERY
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The present invention relatesto a nanoparticle having a size comprised from 2 to 300 nm comprising: (i) a core comprising on its surface a noble metal selected from gold, silver or platinum, and (ii) an optionally positively charged amphiphilic linker comprising a hydrophobic C1-C20 alkyl thiolate moiety and a hydrophilic moietywhich is optionally hydrophilic positively charged. The invention also provides nanovectors comprising the nanoparticles of the invention and a compound of interest,such as a pharmaceutically active agent, in particular an anti-tumoral agent. Also provided are nanoparticles and nanovectors as defined above for diagnosis or for the prevention and/or treatment of a disease, in particular cancer.
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- A novel biocompatible europium ligand for sensitive time-gated immunodetection
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We describe the synthesis of a novel hydrophilic derivative of a tetradentate β-diketone europium ligand that was used to prepare an immunoconjugate probe against Giardia lamblia cysts. We used a Gated Autosynchronous Luminescence Detector (GALD) to obtain high quality delayed luminescence images of cells 30-fold faster than ever previously reported.
- Sayyadi, Nima,Connally, Russell E.,Try, Andrew
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p. 1154 - 1157
(2016/01/15)
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- Directed interactions of block copolypept(o) ides with mannose-binding receptors: Peptomicelles targeted to cells of the innate immune system
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Core-shell structures based on polypept(o)ides combine stealth-like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn)) have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside as initiator in the sequential ring-opening polymerization of α-amino acid N-carboxyanhydrides. These amphiphilic block copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.
- Heller, Philipp,Mohr, Nicole,Birke, Alexander,Weber, Benjamin,Reske-Kunz, Angelika,Bros, Matthias,Barz, Matthias
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- Covalent Protein Labeling by Enzymatic Phosphocholination
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We present a new protein labeling method based on the covalent enzymatic phosphocholination of a specific octapeptide amino acid sequence in intact proteins. The bacterial enzyme AnkX from Legionella pneumophila has been established to transfer functional phosphocholine moieties from synthetically produced CDP-choline derivatives to N-termini, C-termini, and internal loop regions in proteins of interest. Furthermore, the covalent modification can be hydrolytically removed by the action of the Legionella enzyme Lem3. Only a short peptide sequence (eight amino acids) is required for efficient protein labeling and a small linker group (PEG-phosphocholine) is introduced to attach the conjugated cargo.
- Heller, Katharina,Ochtrop, Philipp,Albers, Michael F.,Zauner, Florian B.,Itzen, Aymelt,Hedberg, Christian
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p. 10327 - 10330
(2015/09/01)
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- Lactose as a "trojan horse" for quantum dot cell transport
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A series of glycan-coated quantum dots were prepared to probe the effect of glycan presentation in intracellular localization in HeLa and SV40 epithelial cells. We show that glycan density mostly impacts on cell toxicity, whereas glycan type affects the cell uptake and intracellular localization. Moreover, we show that lactose can act as a "Trojan horse" on bi-functionalized QDs to help intracellular delivery of other non-internalizable glycan moieties and largely avoid the endosomal/lysosomal degradative pathway. With a spoonful of sugar. Glycan-coated quantum dots were used to probe the effect of glycan presentation in intracellular localization in HeLa and SV40 epithelial cells. Glycan density was found to mostly impact cell toxicity, whereas glycan type affects cell uptake and intracellular localization. Also, lactose was found to help the intracellular delivery of other non-internalizable glycan moieties. Copyright
- Benito-Alifonso, David,Tremel, Shirley,Hou, Bo,Lockyear, Harriet,Mantell, Judith,Fermin, David J.,Verkade, Paul,Berry, Monica,Galan, M. Carmen
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p. 810 - 814
(2014/01/23)
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- Development of a long acting human growth hormone analog suitable for once a week dosing
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Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model.
- Palanki, Moorthy S.S.,Bhat, Abhijit,Bolanos, Ben,Brunel, Florence,Del Rosario, Joselyn,Dettling, Danielle,Horn, Mark,Lappe, Rodney,Preston, Ryan,Sievers, Annette,Stankovic, Nebojsa,Woodnut, Gary,Chen, Gang
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p. 402 - 406
(2013/02/23)
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- Synthesis of a four-component [3]catenane using three distinct noncovalent interactions
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A multicomponent assembly is described resulting in [2] and [3]catenanes using three flexible components and three distinct noncovalent interactions. Despite the possibility of competing side-products, only the desired assemblies are generated and characterized spectroscopically. The Royal Society of Chemistry.
- Alemán García, Miguel á.,Bampos, Nick
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supporting information
p. 27 - 30
(2013/02/23)
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- DYE COMPOSITIONS, METHODS OF PREPARATION, CONJUGATES THEREOF, AND METHODS OF USE
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Dye compounds of the formula (1) wherein A is a protective agent group that has a characteristic of modifying the singlet-triplet occupancy of the shown cyanine moiety, and M is a reactive crosslinking group or a group that can be converted to a reactive crosslinking group. Methods for synthesizing the dye compounds and applications for their use are also described.
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- Photoactivable nonsymmetrical bifunctional linkers for protein immobilization on attenuated total reflectance FTIR optical devices
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The photosensitive 4-azido-2,3,5,6-tetrafluoro-1-benzoyl core has been connected to maleimide-, chloroacetyloxy-, or succinimidyl carbonate motifs through various spacers to furnish a series of bifunctional linkers. One linker (7a) has been used for the construction of a biosensor for β-lactam antibiotic detection by attenuated total reflectance FTIR (ATR-FTIR) spectroscopy. Linkers featuring a photosensitive aryl azide motif at one end and a function reactive toward nucleophiles at the other end are described. One linker is used for the construction of a biosensor for β-lactam antibiotic detection by attenuated total reflectance FTIR spectroscopy. Copyright
- Hammaecher, Catherine,Joris, Bernard,Goormaghtigh, Erik,Marchand-Brynaert, Jacqueline
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p. 7952 - 7959
(2014/01/06)
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- Strapped-porphyrin-based molecular turnstiles
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The synthesis of a series of molecular turnstiles that contained both H-bond-donor and -acceptor sites was achieved. Their structures were based on tetra-aryl X2SnIV porphyrins (X=Cl or OH) as H-bond-acceptor sites that were equipped with a rotor that contained a pyridyldiamide moiety as a H-bond donor. In the solution phase, 1D and 2D NMR spectroscopic analysis showed that switching between the closed state, which resulted from the formation of intramolecular H-bonds, and the open state of the turnstile was achieved by using external H-bond-acceptor molecules, such as DMSO. The solid-state structure of the closed state of the turnstile was established by single-crystal X-ray diffraction. Re-turn to sender: Molecular turnstiles, which were based on strapped-type tetra-aryl X2Sn IV porphyrins (X=Cl or OH) that contained both H-bond-donor and -acceptor sites, were prepared; switching between their open and closed states was studied in solution by 1D and 2D NMR spectroscopy. Copyright
- Lang, Thomas,Graf, Ernest,Kyritsakas, Nathalie,Hosseini, Mir Wais
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experimental part
p. 10419 - 10426
(2012/10/08)
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- SYNTHESIS OF OBTAINING MODIFIED POLYETHYLENE GLYCOL INTERMEDIATES
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The present invention provides novel and more efficient synthesis's for obtaining an intermediate in the synthesis of obtaining a protecting group aminoxy PEG linker.
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Page/Page column 11
(2012/01/14)
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- Unmasking photolithography: A versatile way to site-selectively pattern gold substrates
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Surface chemistry: A new method for creating complex patterns on gold substrates is reported. Substrates were functionalized with nitroveratryl- protected carboxylic acid and hydroxy-terminated thiol monomers and patterned with a direct-write photolithography system to produce complex functional group gradients. In addition, two amine molecules were sequentially coupled on the substrate under spatial control (see picture). Copyright
- Hynes, Matthew J.,Maurer, Joshua A.
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p. 2151 - 2154
(2012/04/05)
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- Preparation of carbohydrate arrays by using Diels-Alder reactions with inverse electron demand
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Carbohydrate microarrays are an emerging tool for the high-throughput screening of carbohydrate-protein interactions that represent the basis of many biologically and medicinally relevant processes. The crucial step in the preparation of carbohydrate arrays is the attachment of carbohydrate probes to the surface. We examined the Diels-Alder reaction with inverse-electron-demand (DARinv) as an irreversible, chemoselective ligation reaction for that purpose. After having shown the efficiency of the DARinv in solution, we prepared a series of carbohydrate-dienophile conjugates that were printed onto tetrazine-modified glass slides. Binding experiments with fluorescently labeled lectins proved successful and homogeneous immobilization was achieved by the DARinv. For immobilization of nonfunctionalized reducing oligosaccharides we developed a bifunctional chemoselective linker that enabled the attachment of a dienophile tag to the oligosaccharides through oxime ligation. The conjugates obtained were successfully immobilized on glass slides. The presented strategies for the immobilization of both synthetic carbohydrate derivatives and unprotected reducing oligosaccharides facilitate the preparation of high-quality carbohydrate microarrays by means of the chemoselective DARinv. This concept can be readily adapted for the preparation of other biomolecule arrays. Copyright
- Beckmann, Henning S. G.,Niederwieser, Andrea,Wiessler, Manfred,Wittmann, Valentin
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p. 6548 - 6554
(2012/06/30)
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- LYOTROPIC CHROMOPHORIC COMPOUNDS, LIQUID CRYSTAL SYSTEMS AND OPTICALLY ANISOTROPIC FILMS
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Lyotropic chromophoric compounds comprised of a naphthalimide derivative, a perylene-3,4-dicarboxylic imide derivative, or a perylenetetracarboxylic diimide derivative are described. The compounds can be used to form liquid crystal systems possessing high quality optical properties. The resulting liquid crystal systems are readily applied onto a substrate to obtain optically isotropic or anisotropic, at least partially crystalline films applicable in various fields.
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- Zinc(II)cyclen-peptide conjugates interacting with the weak effector binding state of Ras
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Zinc(II)cyclen-peptide hybrid compounds and bis-zinc(II)cyclen complexes are prepared as potential binders of the guanine nucleotide binding protein Ras, an important molecular switch in cellular signal transduction. The design of the compounds is based on the previous observation that zinc(II)cyclen complexes could serve as lead compounds for inhibitors of Ras-effector interaction and thus be able to interrupt Ras induced signal transduction. Zinc(II)cyclen selectively stabilizes conformational state 1 of active Ras, a conformational state with drastically decreased affinity to effector proteins like Raf-kinase. To achieve higher binding affinities of such Ras-Raf interaction inhibitors, zinc(II)cyclen conjugates with short peptides, derived from the sequence of the Ras-activator SOS, were prepared by solid phase synthesis protocols. Dinuclear bis-zinc(II)cyclen complexes were obtained from alkyne-azide cycloaddition reactions. NMR investigations of the prepared compounds revealed that the peptide conjugates do not lead to an increase in Ras binding affinity of the metal complex-peptide conjugates. The dinuclear zinc complexes lead to an immediate precipitation of the protein prohibiting spectroscopic investigations of their binding.
- Schmidt, Florian,Rosnizeck, Ina C.,Spoerner, Michael,Kalbitzer, Hans Robert,K?nig, Burkhard
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- Copper-catalyzed azide-alkyne cycloaddition in the synthesis of polydiacetylene: "click glycoliposome" as biosensors for the specific detection of lectins
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Supramolecular self-assembly of conjugated diacetylenic amphiphile-tethered ligands photopolymerize to afford polydiacetylene (PDA) functional liposomes. Upon specific interaction with a variety of biological analytes in aqueous solution, PDA exhibits rapid colorimetric transitions. The PDA nanoassemblies, which are excellent membrane mimics, include an ene-yne polymeric reporter responsible for the chromatic transitions and the molecular recognition elements that are responsible for selective and specific binding to the biological target. A bottleneck in the fabrication of these colorimetric biosensors is the preparation of the diacetylenic monomer embedded with the recognition element of choice. In the present work, we make use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as key step in the preparation of sugar-coated liposome biosensors. The regioselective click ligation of the triacetylenic N-(2-propynyl)pentacosa-10,12-diynamide (NPPCDAM) with a variety of mannose-and lactose-tethered azides afforded chemo-and regioselectively the corresponding 1,2,3-triazole. The obtained diacetylenic monomers were incorporated efficiently into vesicles to afford functional mannose-and lactose-coated glycoliposomes. The obtained PDA-based click glycoliposomes have been characterized by using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and UV/Vis spectroscopy. The efficiency of the reported approach was demonstrated by the rapid optimization of the hydrophilic spacer between the lipidic matrix and the mannose head group for the colorimetric detection of Concavalina A.
- Leal, Manuel Pernia,Assali, Mohyeddin,Fernandez, Inmaculada,Khiar, Noureddine
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p. 1828 - 1836
(2011/03/22)
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- Functional virus-based polymer-protein nanoparticles by atom transfer radical polymerization
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Viruses and virus-like particles (VLPs) are useful tools in biomedical research. Their defined structural attributes make them attractive platforms for engineered interactions over large molecular surface areas. In this report, we describe the use of VLPs as multivalent macroinitiators for atom transfer radical polymerization. The introduction of chemically reactive monomers during polymerization provides a robust platform for post-synthetic modification via the copper-catalyzed azide-alkyne cycloaddition reaction. These results provide the basis to construct nanoparticle delivery vehicles and imaging agents using protein-polymer conjugates.
- Pokorski, Jonathan K.,Breitenkamp, Kurt,Liepold, Lars O.,Qazi, Shefah,Finn
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p. 9242 - 9245
(2011/08/06)
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- Synthesis of biotin-containing phosphoramidite linker with polyether spacer arm
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A phosphoramidite linker unit, based on glycerol backbone and containing a biotin residue attached through a tetraethylene glycol spacer arm, was synthesized. DMTr-Glycidol and tetraethylene glycol were used as starting materials. After conversion of one of hydroxy groups in tetraethylene glycol into an amino group, the epoxy cycle in DMTr-glycidol was opened by this amino alcohol, resulting in the corresponding ether and some quantity of secondary amine. After attaching of biotin residue to the ether followed by phosphitylation, the desirable linker was obtained. The structure of the linker was confirmed by 1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC, 1H-15N HSQC, and 1H-15N HMBC spectra. The resulted phosphoramidite linker unit is suitable for use in common DNA synthesizers. This approach can be used for preparation of various modifiers containing reporter groups attached to the primary amino function using conventional procedures. Copyright Taylor and Francis Group, LLC.
- Kayushin, Alexey,Demekhina, Alexandra,Korosteleva, Maria,Miroshnikov, Anatoly,Azhayev, Alex
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p. 490 - 502
(2011/12/16)
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- A convenient route to diversely substituted icosahedral closomer nanoscaffolds
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The design and synthesis of icosahedral polyhedral borane closomer motifs based upon carbonate and carbamate anchoring groups for biomedical applications are described. Dodecacarbamate closomers containing easily accessible groups of interest at their linker termini were synthesized via activation of the B-OH vertices as aryl carbonates and their subsequent reaction with primary amines. Novel dodecacarbonate closomers were successfully synthesized for the first time by reacting [closo-B12(OH)12]2- with an excess of respective aryl chloroformates, utilizing relatively short reaction times, mild conditions and simple purification strategies, all of which had previously presented difficulties in closomer chemistry. This methodology for the 12-fold degenerate synthesis of carbonate and carbamate closomers will greatly facilitate further exploration of closomers as monodisperse nanomolecular delivery platforms.
- Jalisatgi, Satish S.,Kulkarni, Vikas S.,Tang, Betty,Houston, Zachary H.,Lee, Mark W.,Hawthorne, M. Frederick
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supporting information; scheme or table
p. 12382 - 12385
(2011/10/02)
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- SYNTHESIS OF A PEG-6 MOIETY FROM COMMERCIAL LOW-COST CHEMICALS
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The present invention provides novel synthesis's for obtaining a protecting group aminoxy PEG-6 linker from cost effective, and readily available starting materials and chemicals or modified polyethylene glycols. More specifically, a novel synthesis of obtaining a modified Boc-protected aminoxy PEG-6 linker was achieved so that said linker may be attached to a vector such as a peptide based fragment.
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Page/Page column 24; 25
(2009/10/21)
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- Potent ligands for prokaryotic UDP-galactopyranose mutase that exploit an enzyme subsite
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UDP-Galactopyranose mutase (UGM or Glf), which catalyzes the interconversion of UDP-galactopyranose and UDP-galactofuranose, is implicated in the viability and virulence of multiple pathogenic microorganisms. Here we report the synthesis of high-affinity ligands for UGM homologues from Klebsiella pneumoniae and Mycobacterium tuberculosis. The potency of these compounds stems from their ability to access both the substrate binding pocket and an adjacent site.
- Dykhuizen, Emily C.,Kiessling, Laura L.
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supporting information; experimental part
p. 193 - 196
(2009/06/28)
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- INHIBITORS OF UDP-GALACTOPYRANOSE MUTASE THWART MYCOBACTERIAL GROWTH
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Compounds which inhibit microbial growth or attenuate the virulence of pathogen microorganisms. Compounds of the invention inhibit UDP-galactopyranose mutase (UGM) and have activity as inhibitors of microbial growth of microorganisms which contain this enzyme and particularly those microorganisms in which this enzyme is responsible for the incorporation of galactofuranose residues, particularly for uridine 5'-diphosphate (UDP) galactopyranose mutase. Compounds of the invention inhibit UDP- galactopyranose mutase (UGM) and have activity to attenuate virulence of pathogenic microorganisms, including mycobacteria.
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Page/Page column 66
(2009/12/05)
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- Tailoring carbon nanotube surfaces with glyconanorings: New bionanomaterials with specific lectin affinity
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Remarkably stable, water-soluble glyconanoring-coated SWCNTs were prepared by self organization and photopolymerization of neutral diacetylene-based glycolipids on the nanotube surface; the nanoconstructs are able to engage in specific ligand-lectin interactions in a similar way to glycoconjugates on cell membranes.
- Khiar, Noureddine,Leal, Manuel Pernia,Baati, Rachid,Ruhlmann, Christine,Mioskowski, Charles,Schultz, Patrick,Fernandez, Inmaculada
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supporting information; experimental part
p. 4121 - 4123
(2009/12/25)
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- Polymer-supported cationic templates for molecular recognition of anionic hosts in water
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Translocating solution-phase molecular recognition of oppositely charged hosts and guests to the solid phase represents a major challenge; we report a successful immobilisation strategy which allows selective host-guest interactions in water unencumbered by unwanted ion exchange-type interactions. The Royal Society of Chemistry.
- Besenius, Pol,Cormack, Peter A. G.,Ludlow, R. Frederick,Otto, Sijbren,Sherrington, David C.
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supporting information; scheme or table
p. 2809 - 2811
(2009/02/05)
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- Foldable polymers as probes
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Disclosed herein are novel probes, which can be used to detect and identify target molecules of interest in a sample. The disclosed probes can be used to monitor conformational changes induced by molecular recognition events in addition to providing signaling the presence and/or identity of a target molecule. Methods, including solid phase synthesis techniques, for making probe molecules that exhibit changes in their optical properties upon target molecule binding are described in the disclosure. Also disclosed herein are novel chromophore moieties, which have tailored fluorescent emission spectra.
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Page/Page column 17
(2008/06/13)
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- GALACTOSE DERIVATIVE, DRUG CARRIER AND MEDICINAL COMPOSITION
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The object of the invention is to provide a novel and useful galactose derivative constituting a drug carrier by which a medicine can be efficiently transferred into the liver, a drug carrier comprising the derivative, and a pharmaceutical composition comprising the carrier and a medicine. The present invention relates to a galactose derivative made up of galactose, a suitable spacer and a certain lipid, a drug carrier comprising the derivative and a cationic lipid, and a pharmaceutical composition comprising the carrier and a medicine (preferably a double strand RNA, a double strand DNA, an oligo nucleic acid) .
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Page/Page column 22
(2010/11/27)
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- To fold or to assemble?
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We introduce a new class of foldable oligomers consisting of alternating rigid and flexible regions. The rigid segments overlap to give π-stacked folded conformers whose formation is driven mostly by π-π molecular orbital overlaps. As the oligomer concentration increases, the folded molecular structures further self-assemble into larger nanostructures. The dynamic processes of folding and self-organization are monitored with absorption, fluorescence, and NMR spectroscopies. Our results show that folding dominates at low concentrations (1~ mM) and precedes self-assembly, which occurs over the initial concentration range of 1-100 mM. Copyright
- Wang, Wei,Li, Lin-Song,Helms, Greg,Zhou, Hong-Hui,Li, Alexander D. Q.
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p. 1120 - 1121
(2007/10/03)
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- 1H NMR investigation of solvent effects in aromatic stacking interactions
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One of the marquis challenges in modern Organic Chemistry concerns the design and synthesis of abiotic compounds that emulate the exquisite complex structures and/or functions of biological macromolecules. Oligomers possessing the propensity to adopt well-defined compact conformations, or foldamers, have been attained utilizing hydrogen bonding, torsional restriction, and solvophobic interactions. In this laboratory, aromatic electron donor-acceptor interactions have been exploited in the design of aedamers-foldamers that adopt a novel, pleated secondary structure in aqueous solution. Herein is reported detailed 1H NMR binding studies of aedamer monomers that were carried out in solvents and solvent mixtures covering a broad polarity range. Curve-fitting analysis of the binding data using a model that incorporated the formation of higher order and self-associated complexes yielded a linear free energy relationship between the free energy of complexation and the empirical solvent polarity parameter, ET(30). From these studies, the association of electron-rich and electron-deficient aedamer monomers was seen to be driven primarily by hydrophobic interactions in polar solvents. However, the magnitude of these interactions is modulated to a significant extent by the geometry of the donor-acceptor complex, which, in turn, is dictated by the electrostatic complementarity between the electron-deficient and electron-rich aromatic faces of the monomers.
- Cubberley,Iverson
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p. 7560 - 7563
(2007/10/03)
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- Synthesis of a series of oligo(ethylene glycol)-terminated alkanethiol amides designed to address structure and stability of biosensing interfaces
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A strategy for the synthesis of a series of closely related oligo(ethylene glycol)-terminated alkanethiol amides (principally HS(CH2)mCONH(CH2CH2O) nH; m = 2, 5, 11, 15, n = 1, 2, 4, 6, 8, 10, 12) and analogous esters has been developed. These compounds were made to study the structure and stability of self-assembled monolayers (SAMs) on gold in the prospect of designing new biosensing interfaces. For this purpose, monodisperse heterofunctional oligo(ethylene glycols) with up to 12 units were prepared. Selective monoacylation of the symmetrical tetra- and hexa(ethylene glycol) diols as their mesylates with the use of silver(I) oxide was performed. The synthetic approach was based on carbodiimide couplings of various oligo(ethylene glycol) derivatives to ω-(acetylthio) carboxylic acids via a terminal amino or hydroxyl function. SAM structures on gold were studied with respect to thickness, wettability (water contact angles ~30°), and conformation. A good fit was obtained for the relation between monolayer thickness (d) and the number of units in the oligo(ethylene glycol) chain (n): d = 2.8n + 21.8 (A). Interestingly, the corresponding infrared spectroscopy analysis showed a dramatic change in conformation of the oligomeric chains from all-trans (n = 4) to helical (n ≥ 6) conformation. A crystalline helical structure was observed in the SAMs for n > 6.
- Svedhem,Hollander,Shi,Konradsson,Liedberg,Svensson
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p. 4494 - 4503
(2007/10/03)
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- Synthesis of New Phospholipids Linked to Steroid-Hormone Derivatives Designed for Two-Dimensional Crystallization of Proteins
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The synthesis of phospholipids 1n-3n, rationally designed for two-dimensional crystallization of progesterone and estradiol receptors, is reported.The structure of theses lipids provides them with essential properties such as fluidity and stability when spread into monolayers at the air/H2O interface, affinity for the protein to be crystallized, and accessibility of the ligand under the lipid monolayer.
- Lebeau, Luc,Oudet, Pierre,Mioskowski, Charles
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p. 1697 - 1706
(2007/10/02)
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- Precursor to nucleic acid probe
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Nucleic acids may be labeled by intercalating the alkylating intercalation moiety of a labeling reagent into a partially double-stranded nucleic acid to form a complex and activating the complex to cause covalent bonding between the reagent and the nucleic acid. Preferably, the labeled nucleic acid is a hybridization probe for detecting nucleic acid sequences capable of hybridizing with a hybridizing region of the nucleic acid. Also preferably the label moiety is non-radioactive. The labeling reagent is of the formula: where A is an alkylating intercalation moiety, B is a divalent organic moiety of the formula: STR1 where Y is O, NH or N--CHO, x is a number from 1 to 4, y is a number from 2 to 4, and L is a monovalent label moiety, wherein B is exclusive of any portion of the intercalation and label moieties. Preferably A is a 4-methylene-substituted psoralen moiety, and most preferably A is a 4'-methylene-substituted-4,5', 8-trimethylpsoralen moiety and L is biotin. This patent application is a divisional application of copending U.S. Ser. No. 791,332 filed Oct. 25, 1985, now U.S. Pat. No. 4,617,261, which is a continuation-in-part application (CIP) of copending U.S. Ser. No. 683,263 filed Dec. 18, 1984, now U.S. Pat. No. 4,582,789 which is a CIP of copending U.S. Ser. No. 591,811 filed Mar. 21, 1984, now abandoned. This patent application is also related to copending U.S. application Ser. No. 791,323 filed Oct. 25, 1985.
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- REDUCTION D'AZIDES EN AMINES PAR LE FORMIATE D'AMMONIUM PAR "TRANSFERT D'HYDROGENE CATALYSE" (CTH)
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The azides are reduced to amines in very good yields by "Catalytic Transfer Hydrogenation" (CTH) using ammonium formate.
- Gartiser, T.,Selve, C.,Delpuech, J.-J.
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p. 1609 - 1610
(2007/10/02)
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