26150-06-1Relevant academic research and scientific papers
Design of functionalized cellulosic honeycomb films: Site-specific biomolecule modification via "click chemistry"
Xu, William Z.,Zhang, Xinyue,Kadla, John F.
, p. 350 - 357 (2012)
Value-added materials from naturally abundant polymers such as cellulose are of significant importance. In particular, cellulosic open-framework structures with controlled chemical functionality of the internal surface have great potential in many biosens
Catenation through a Combination of Radical Templation and Ring-Closing Metathesis
Gibbs-Hall, Ian C.,Vermeulen, Nicolaas A.,Dale, Edward J.,Henkelis, James J.,Blackburn, Anthea K.,Barnes, Jonathan C.,Stoddart, J. Fraser
, p. 15640 - 15643 (2015)
Synthesis of an electrochemically addressable [2]catenane has been achieved following formation by templation of a [2]pseudorotaxane employing radically enhanced molecular recognition between the bisradical dication obtained on reduction of the tetracationic cyclophane, cyclobis(paraquat-p-phenylene), and the radical cation generated on reduction of a viologen disubstituted with p-xylylene units, both carrying tetraethylene glycol chains terminated by allyl groups. This inclusion complex was subjected to olefin ring-closing metathesis, which was observed to proceed under reduced conditions, to mechanically interlock the two components. Upon oxidation, Coulombic repulsion between the positively charged and mechanically interlocked components results in the adoption of a co-conformation where the newly formed alkene resides inside the cavity of the tetracationic cyclophane. 1H NMR spectroscopic analysis of this hexacationic [2]catenane shows a dramatic upfield shift of the resonances associated with the olefinic and allylic protons as a result of them residing inside the tetracationic component. Further analysis shows high diastereoselectivity during catenation, as only a single (Z)-isomer is formed.
Stereoselective synthesis of a topologically chiral molecule: The trefoil knot
Perret-Aebi, Laure-Emmanuelle,Von Zelewsky, Alexander,Dietrich-Buchecker, Christiane,Sauvage, Jean-Pierre
, p. 4482 - 4485 (2004)
Tying nice neat knots is demonstrated on a molecular level with the stereoselective synthesis of a trefoil knot. The key reaction was the completely stereoselective formation of a double-stranded helical precursor from two pinene-bipyridine threads around two CuI centers (the pinene moieties contain stereogenic centers). The helix was then transformed through several steps into 1; demetallation of the complex 1 yielded the configurationally predetermined free trefoil knot.
Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel-Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7
Zoppi, Vittoria,Hughes, Scott J.,Maniaci, Chiara,Testa, Andrea,Gmaschitz, Teresa,Wieshofer, Corinna,Koegl, Manfred,Riching, Kristin M.,Daniels, Danette L.,Spallarossa, Andrea,Ciulli, Alessio
, p. 699 - 726 (2019/01/11)
Developing PROTACs to redirect the ubiquitination activity of E3 ligases and potently degrade a target protein within cells can be a lengthy and unpredictable process, and it remains unclear whether any combination of E3 and target might be productive for degradation. We describe a probe-quality degrader for a ligase-target pair deemed unsuitable: the von Hippel-Lindau (VHL) and BRD9, a bromodomain-containing subunit of the SWI/SNF chromatin remodeling complex BAF. VHL-based degraders could be optimized from suboptimal compounds in two rounds by systematically varying conjugation patterns and linkers and monitoring cellular degradation activities, kinetic profiles, and ubiquitination, as well as ternary complex formation thermodynamics. The emerged structure-activity relationships guided the discovery of VZ185, a potent, fast, and selective degrader of BRD9 and of its close homolog BRD7. Our findings qualify a new chemical tool for BRD7/9 knockdown and provide a roadmap for PROTAC development against seemingly incompatible target-ligase combinations.
Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect
Xiao, Qiang,Bécar, Natalie A.,Brown, Nathaniel P.,Smith, Mason S.,Stern, Kimberlee L.,Draper, Steven R.E.,Thompson, Katherine P.,Price, Joshua L.
supporting information, p. 8933 - 8939 (2018/12/10)
Hydrocarbon stapling and PEGylation are distinct strategies for enhancing the conformational stability and/or pharmacokinetic properties of peptide and protein drugs. Here we combine these approaches by incorporating asparagine-linked O-allyl PEG oligomers at two positions within the β-sheet protein WW, followed by stapling of the PEGs via olefin metathesis. The impact of stapling two sites that are close in primary sequence is small relative to the impact of PEGylation alone and depends strongly on PEG length. In contrast, stapling of two PEGs that are far apart in primary sequence but close in tertiary structure provides substantially more stabilization, derived mostly from an entropic effect. Comparison of PEGylation + stapling vs. alkylation + stapling at the same positions in WW reveals that both approaches provide similar overall levels of conformational stability.
TAU-PROTEIN TARGETING PROTACS AND ASSOCIATED METHODS OF USE
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Paragraph 1461, (2018/05/24)
The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
NOVEL TRIAZINE COMPOUND, ALL-SOLID-STATE POLYMER ELECTROLYTE COMPOSITION AND USE THEREOF
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Paragraph 0123; 0139-0142, (2018/04/12)
The present invention relates to a novel triazine compound represented by chemical formula 1, an all-solid-state polymer electrolyte composition comprising the same as a cross-linking agent and uses thereof. More specifically, the triazine compound effectively inhibits crystallization of a plasticizer at a low temperature (room temperature) to show significantly improved ion conductivity, and can realize significantly improved electrochemical stability and excellent battery properties, thereby being usefully used as an all-solid-state polymer electrolyte composition such as a lithium-polymer secondary battery, a dye-sensitized solar cell, etc.COPYRIGHT KIPO 2018
Integrating Epigenetic Modulators into NanoScript for Enhanced Chondrogenesis of Stem Cells
Patel, Sahishnu,Pongkulapa, Thanapat,Yin, Perry T.,Pandian, Ganesh N.,Rathnam, Christopher,Bando, Toshikazu,Vaijayanthi, Thangavel,Sugiyama, Hiroshi,Lee, Ki-Bum
supporting information, p. 4598 - 4601 (2015/04/27)
N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB) is a small molecule that functions by altering the chromatin architecture to modulate gene expression. We report a new CTB derivative with increased solubility and demonstrate CTB's functionality by conjugating it on the recently established NanoScript platform to enhance gene expression and induce stem cell differentiation. NanoScript is a nanoparticle-based artificial transcription factor that emulates the structure and function of transcription factor proteins (TFs) to effectively regulate endogenous gene expression. Modifying NanoScript with CTB will more closely replicate the TF structure and enhance CTB functionality and gene expression. To this end, we first conjugated CTB onto NanoScript and initiated a time-dependent increase in histone acetyltransferase activity. Next, because CTB is known to trigger the pathway involved in regulating Sox9, a master regulator of chondrogenic differentiation, we modifed a Sox9-specific NanoScript with CTB to enhance chondrogenic gene activity and differentiation. Because NanoScript is a tunable and robust platform, it has potential for various gene-regulating applications, such as stem cell differentiation.
Controlled-length efficient synthesis of heterobifunctionalized oligo ethylene glycols
Zona, Cristiano,D'Orazio, Giuseppe,La Ferla, Barbara
supporting information, p. 709 - 712 (2013/05/09)
A set of heterobifunctional oligo ethylene glycols have been synthesized in a straightforward and stepwise manner starting from inexpensive, commercially available, tetraethylene glycol. Introduction of terminal allyl moieties followed by reductive ozonolysis allowed controlled elongation. Mono-allyl derivatives were used for the elongation with a functionalized moiety and for successive introduction of different functional groups on the chain terminal. Georg Thieme Verlag Stuttgart - New York.
OLEFIN METATHESIS REACTIONS OF AMINO ACIDS, PEPTIDES AND PROTEINS CONTAINING ALLYL SULFIDE GROUPS
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Page/Page column 13, (2012/07/27)
A method for the modification of an amino acid, protein or peptide is disclosed. The method comprises reacting a carbon-carbon double bond-containing compound with an amino acid, a protein or a peptide containing an allyl sulfide group in the presence of a catalyst which promotes olefin metathesis, to form a modified amino acid, protein or peptide. Preferred carbon-carbon double bond-containing compounds include carbohydrates.
