- PROTAC-mediated degradation of class i histone deacetylase enzymes in corepressor complexes
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We have identified a proteolysis targeting chimera (PROTAC) of class I HDACs 1, 2 and 3. The most active degrader consists of a benzamide HDAC inhibitor, an alkyl linker, and the von Hippel-Lindau E3 ligand. Our PROTAC increased histone acetylation levels and compromised colon cancer HCT116 cell viability, establishing a degradation strategy as an alternative to class I HDAC inhibition.
- Adams, Grace E.,Cowley, Shaun Michael,Hodgkinson, James T.,Millard, Christopher J.,Norris, James K. S.,Schwabe, John W. R.,Smalley, Joshua P.,Song, Yun
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supporting information
p. 4476 - 4479
(2020/05/13)
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- Engineered peptidic constructs metabolize amyloid β by self-assembly-driven reactions
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Inspired by the unique mechanism of proteolytic maturation of host cell factor-1, we designed small peptide-based constructs that selectively recognized amyloid β (Aβ) and cleaved it in a non-catalytic manner initially around the α-secretase cleavage-site, thus termed as "artificial α-secretases". "Artificial α-secretases" also cleaved Aβ on the cleavage-sites of other Aβ processing enzymes by prolonged treatment, as evidenced by time-resolved MALDI-TOF-mass analyses.
- Mondal, Tanmay,Mandal, Bhubaneswar
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supporting information
p. 4933 - 4936
(2019/05/21)
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- FIBER COATED NANOPORES
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Provided herein are compositions, compounds, processes, and methods of use of 3D porous coating(s) on or near a nanopore(s) for analysis or detection of charged polymers such as nucleic acids, proteins, protein-nucleic acid complexes, small molecule-biological complexes, polymer-biological complexes, and/or polyelectrolytes.
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Paragraph 0475
(2016/07/05)
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- Hybrids of acylated homoserine lactone and nitric oxide donors as inhibitors of quorum sensing and virulence factors in Pseudomonas aeruginosa
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Pseudomonas aeruginosa is an opportunistic pathogen causing a variety of life-threatening diseases such as cystic fibrosis and nosocomial infections in burn victims. The ability of P. aeruginosa to cause infection is attributed to the production of virulence factors such as pyocyanin and elastases. These virulence factors are under the control of quorum sensing (QS) a cell to cell communication process controlled by small diffusible signalling molecules based on N-acyl-homoserine lactones (AHLs) known as autoinducers. The inhibition of QS and thereby virulence factors is seen as a potential new anti-infective strategy. Additionally, the role of nitric oxide (NO) in downstream processes in bacteria such as biofilm dispersal, motility, virulence and antimicrobial defence systems is gaining attention and could be used to control bacterial. Herein we report the design and synthesis of hybrid compounds based on AHL signalling molecules and NO donors as anti-infective agents. A series of AHL-NO hybrids were synthesised and potent inhibitors of QS and virulence factors of P. aeruginosa were identified. This research has led to conversion of agonist AHLs to antagonist AHLs with dual properties of QS inhibition and NO release.
- Kutty, Samuel K.,Barraud, Nicolas,Ho, Kitty K. K.,Iskander, George M.,Griffith, Renate,Rice, Scott A.,Bhadbhade, Mohan,Willcox, Mark D. P.,Black, David Stc,Kumar, Naresh
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p. 9850 - 9861
(2015/10/05)
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- NOVEL FLAVONOID COMPOUNDS AND USES THEREOF
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The present disclosure provides a compound of the following formula, racemates, enantiomers, prodrugs and salts thereof: Formula (I). Also provided is the use of these compounds for the treatment of ischemia and reperfusion injuries. Further applications include the treatment of diseases caused by cell apoptosis and / or cell necrosis.
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Paragraph 123; 156-157
(2014/05/07)
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- The non-metathetic role of Grubbs' carbene complexes: From hydrogen-free reduction of α,β-unsaturated alkenes to solid-supported sequential cross-metathesis/reduction
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An efficient and high-yielding "hydrogen-free" reduction of α,β-unsaturated alkenes was carried out employing Grubbs' catalyst in a non-metathetic role and Et3SiH. Conditions were optimized under microwave irradiation. Application to the solid-phase organic synthesis allows a facile construction of sp3-sp3 carbon bonds through a sequential cross metathesis/olefin reduction.
- Poeylaut-Palena, Andres A.,Testero, Sebastian A.,Mata, Ernesto G.
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supporting information; experimental part
p. 1565 - 1567
(2011/03/20)
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- Synthesis of cellulose adipate derivatives
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Cellulose esters containing adipates and other ester groups are synthesized by the reaction of commercially available cellulose esters in solution with the benzyl monoester of adipoyl chloride. The products, cellulose adipate esters in which the distal en
- Kar, Nilanjana,Liu, Haoyu,Edgar, Kevin J.
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experimental part
p. 1106 - 1115
(2012/03/08)
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- Drug release from hydrazone-containing peptide amphiphiles
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Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine ε-amine allowed for precis
- Matson, John B.,Stupp, Samuel I.
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supporting information; experimental part
p. 7962 - 7964
(2011/09/13)
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- Esterification of dicarboxylic acids with benzyl alcohol under the action of the microwave radiation
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Reaction of dicarboxylic acid with benzyl alcohol under the microwave irradiation proceeds faster as compared to the thermal conditions. The main reaction products are alkyl dicarboxylates, and the monoester and dibenzyl ether are formed as the side products. A proposal about the nature of the nonthermal effect in the reactions stimulated by the microwave irradiation is considered.
- Aver'yanov,Batrakova,Samuilov,Spiridonova,Kochnev,Galibeev,Gnezdilov
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experimental part
p. 1920 - 1923
(2009/02/08)
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- Films and Particles
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Described herein are compounds and processes that can be used to prepare polymer-based films, particles, gels and related compositions, and processes for delivery of agents, and other uses.
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Page/Page column 41
(2008/06/13)
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- Synergism of microwaves and immobilized enzyme catalysis in synthesis of adipic acid esters in nonaqueous media
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Low-energy microwave irradiation leads to enhancement by a factor of up to 2.63 in comparison with conventional heating in immobilized lipase-catalyzed esterification of adipic acid with various alcohols and this effect is due to the greater frequency of collision, without any change in activation energy of the two modes of heating. Copyright Taylor & Francis, Inc.
- Yadav, Ganapati D.,Lathi, Piyush S.
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p. 1699 - 1705
(2007/10/03)
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- Production and use of derivatized homoserine lactones
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The present invention provides analogues of autoinducer molecules that are derivatized to allow their attachment to other molecules and surfaces. Libraries of the autoinducer analogues are also contemplated. Also provided are methods for using the compounds of the invention to produce compositions, such as immunoconjugates, antibodies and vaccines, which are useful for treating and preventing disease states in a subject. The compositions of the invention are also useful in various assays, including assessing the autoinducer load in a subject.
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Page column 43
(2008/06/13)
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- Self-assembly and dynamics of [2]- and [3]rotaxanes with a dinuclear macrocycle containing reversible Os-N coordinate bonds
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With a dinuclear macrocycle 2 that contains weak reversible OsVI-N coordinate bonds, self-assembly and equilibrium dynamics of [2]- and [3]rotaxanes have been investigated. When the macrocycle 2 was mixed together with threads 4a-e, which all contain an adipamide station but different sizes of end groups, [2]pseudorotaxane- and rotaxane-like complexes were immediately formed with large association constants > of 7 × 103M-1 in CDCl3 at 298 K. Exchange dynamics, explored by 2D-EXSY experiments, suggest that assembly and disassembly of complexes occur through two distinct pathways, slipping or clipping, and this depends on the size of the end groups. The slipping pathway is predominant with smaller end groups that give pseudorotaxane-like complexes, while the clipping pathway is observed with larger end groups that yield rotaxane-like complexes. Under the same conditions, exchange barriers (ΔG≠) were 14.3 kcal mol-1 for 4a and 16.7 kcal mol-1 for 4d, and indicate that the slipping process is at least one order of magnitude faster than the clipping process. Using threads 13a and 13b that contain two adipamide groups, more complicated systems have been investigated in which [2]rotaxane, [3]rotaxane, and free components are in equilibrium. Concentration- and temperature-dependent 1H NMR spectroscopic studies allowed the identification of all possible elements and the determination of their relative distributions in solution. For example, the relative distribution of the free components, [2]rotaxane, and [3]rotaxane are 30, 45, and 25%, respectively, in a mixture of 2 (2mM) and 13a (2mM) in CDCl3, at 10°C. However, [3]rotaxane exists nearly quantitatively in a mixture of 2 (4mM) and 13a (2mM) in CDCl3 at a low temperature - 10°C.
- Chang, Sung-Youn,Choi, Jeung Soon,Jeong, Kyu-Sung
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p. 2687 - 2697
(2007/10/03)
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- Orally effective acid prodrugs of the β-lactamase inhibitor sulbactam
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Sulbactam (1) is a β-lactamase inhibitor with limited oral bioavailability. Lipophilic double-ester prodrug sulbactam pivoxil (2) significantly improves the oral absorption of sulbactam, as does the mutual prodrug double ester sultamicillin (3). We have found that double-ester prodrugs of sulbactam terminating in a carboxyl group (8) also were effective oral-delivery vehicles in rats. Carboxyl-terminated double esters have several potential advantages over their nonionizable lipophilic counterparts, including water solubility, crystallinity, choice of salts for dosage forms, and formation of innocuous byproducts on hydrolysis.
- English,Girard,Jasys,Martingano,Kellogg
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p. 344 - 347
(2007/10/02)
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- SELECTIVE MONOETHERIFICATION AND MONOESTERIFICATION OF DIOLS AND DIACIDS UNDER PHASE-TRANSFER CONDITIONS
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Research on the selectivity of etherification reactions of diols and esterification reactions of diacids by alkyl halides under phase-transfer catalysis has shown that under such conditions, selectivity of monoetherification increases in the order prim sec tert diols, though overall yield of monoether decreases from sec to tert diols.Monoesterification of diacids was accomplished with a high degree of selectivity.Optimal extraction of diols and diacids was found to correspond in general to chain lengths of around 5 carbons.This could mean that the complex formed between the catalyst and the anion to react is stabilized for certain carbon lengths by inner solvation in virtue of its spatial conformation.
- Zerda, Jaime de la,Barak, Gabriela,Sasson, Yoel
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p. 1533 - 1536
(2007/10/02)
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