- OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF
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The present disclosure provides modified oligonucleotides and compositions and methods thereof. In some embodiments, provided technologies comprise modified sugars and/or modified internucleotidic linkages. In some embodiments, the present disclosure provides technologies for preparing modified oligonucleotides. In some embodiments, the present disclosure provides chirally controlled oligonucleotide compositions and methods for their preparation and uses.
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Paragraph 00735-00736
(2021/11/26)
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- Site-Selective Defluorinative sp3C-H Alkylation of Secondary Amides
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A site-selective defluorinative sp3 C-H alkylation of secondary amides that rapidly and reliably incorporates gem-difluoroalkene motifs into previously unfunctionalized sp3 sites is disclosed. This protocol is distinguished by its mild conditions, wide scope, and exquisite site-selectivity, thus unlocking a new platform to introduce carbonyl isosteres at saturated hydrocarbon sites.
- Day, Craig S.,Martin, Ruben,Yue, Wen-Jun
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supporting information
p. 6395 - 6400
(2021/05/29)
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- Rapid Synthesis of Bicyclic N-Heterocyclic Cores from N-Terminal α,β-Unsaturated Diazoketones
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A method for the synthesis of bicyclic N-heterocyclic cores from N-terminal α,β-unsaturated diazoketones has been developed. The transformation involves three sequential steps that include N-deprotection, an intramolecular aza-Michael, and a photochemical Wolff rearrangement as a one-pot protocol. By using this strategy, a series of substituted bicyclic N-heterocycles, particularly, indolizidines and pyrrolizidines, were synthesize in good yields.
- Santiago, Jo?o Victor,Burtoloso, Antonio C. B.
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p. 2822 - 2830
(2018/06/04)
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- Substituent Effects on the pH Sensitivity of Acetals and Ketals and Their Correlation with Encapsulation Stability in Polymeric Nanogels
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The effect of structural variations in acetal- and ketal-based linkers upon their degradation kinetics is studied through the design, synthesis, and study of six series of molecules, comprising a total of 18 different molecules. Through this systematic study, we show that the structural fine-tuning of the linkers allows access to variations in kinetics of degradation of more than 6 orders of magnitude. Hammett correlations show that the ρ value for the hydrolysis of benzylidene acetals is about ?4.06, which is comparable to an SN1-like process. This shows that there is a strong, developing positive charge at the benzylic position in the transition state during the degradation of acetals. This positively charged transition state is consistent with the relative degradation rates of acetals vs ketals (correlated to stabilities of 1°, 2°, and 3° carboxonium ion type intermediates) and the observed effect of proximal electron-withdrawing groups upon the degradation rates. Following this, we studied whether the degradation kinetics study correlates with pH-sensitive variations in the host-guest characteristics of polymeric nanogels that contains these acetal or ketal moieties as cross-linking functionalities. Indeed, the trends observed in the small molecule degradation have clear correlations with the encapsulation stability of guest molecules within these polymeric nanogels. The implications of this fundamental study extend to a broad range of applications, well beyond the polymeric nanogel examples studied here.
- Liu, Bin,Thayumanavan
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p. 2306 - 2317
(2017/02/23)
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- NOVEL LIVER-TARGETING AGENTS AND THEIR SYNTHESIS
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This invention provides novel liver targeting agents and their synthetic methods. A liver targeting agent, with a lysine based nitrilo triacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain is disclosed. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl groups in Nε-benzyloxycarbonyl-Nα-dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 moles of NTA(ahLac)3. This invention also provides a method for adding a spacer between NTA and DTPA. The extended hepatocyte-specific glyco-ligand has higher 111In-radiolabelling yield than those non-extended.
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Page/Page column 1; 2
(2011/04/19)
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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 64
(2009/12/05)
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- REAGENTS FOR LABELLING NUCLEIC ACIDS AND USES THEREOF
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The present invention relates to labelling kits containing novel non-natural nucleotide monomers and to methods of making and using such compounds. The invention further relates to a method of detecting the presence of a nucleic acid, e.g., RNA, of interest in a sample, the method having the following steps: providing the sample; ligating a nucleic acid of interest with a labelling reagent according to the instant invention; providing a nucleic acid array having probes directed to the nucleic acid of interest; hybridizing the labelled nucleic acid fragments to said nucleic acid array; and determining the extent of hybridization to said probes to determine the presence of the nucleic acid of interest.
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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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- Zwitterionic oligonucleotides: A study on binding properties of 2′-O-aminohexyl modifications
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2′-O-Aminohexyl side chains provide excellent conditions for zwitterionic interstrand and intrastrand interactions of oligonucleotides. 2′-O-Aminoalkylated phosphoramidites of adenosine and undine were synthesized and incorporated in increasing number int
- Noe, Christian R.,Winkler, Johannes,Urban, Ernst,Gilbert, Matthias,Haberhauer, Georg,Brunar, Helmut
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p. 1167 - 1185
(2007/10/03)
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- PREPARATION OF ANOMERIC PAIRS OF 1-THIOGLYCOSIDES: USE OF ANOMERIZATION CATALYZED BY BORON TRIFLUORIDE
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Anomeric pairs of some alkyl 1-thioaldopyranosides of D-galactose, D-glucose, D-mannose, 2-acetamido-2-deoxy-D-glucose, 2-acetamido-2-deoxy-D-galactose, and L-fucose were prepared.The per-O-acetylated, 1,2-trans anomers of 6-(trifluoroacetamido)hexyl 1-thioaldopyranosides and 5-(methoxycarbonyl)pentyl 1-thioaldopyranosides were anomerized with boron trifluoride in dichloromethane.The anomeric mixtures were then separated by chromatography, using columns of either silica gel or an ion-exchange resin.De-blocking of the separated compounds provided pure anomers of 6-aminohexyl 1-thioaldopyranosides or 5-carboxypentyl 1-thioaldopyranosides.The aglycons of the latter glycosides were further extended by reaction with aminoacetaldehyde diethyl acetal, which, after deacetalization of the products, provided an ω-aldehydo group.These series of glycosides could be readily coupled to proteins or solid matrices.
- Connolly, Daniel T.,Roseman, Saul,Lee, Yuan C.
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p. 227 - 240
(2007/10/02)
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