- Synthesis of new transglycosidically tethered 5′-nucleotides constrained to a highly biologically relevant profile
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A new motif for restricting 5′-nucleotides to highly biologically relevant conformations has been developed. The 5′,6-oxomethylene transglycosidically tethered versions of uridine 5′-monophosphate and 2′-deoxyuridine 5′-monophosphate (1 and 2, respectively) were synthesized in 10-11 steps from their respective natural nucleoside precursors along routes general to the preparation of tethered versions of a wide variety of 5′-nucleotide-based compounds. In both routes, a shelf-stable 6-hydroxymethyl pyrimidine nucleoside 5′-carboxaldehyde is the key intermediate. It exists in a carbohydrate-like fashion in a cyclic hemiacetal form under aprotic conditions. The phosphorylated cyclic hemiacetals 1 and 2 were isolated as binary mixtures of 5′-diastereomers differing principally in the trajectory of the phosphate group with respect to the carbohydrate. By 1H NMR, both 1 and 2 were demonstrated to be stable to hydrolysis at ambient temperature in D20 solution for at least 2 months. The oxomethylene transglycosidic tether as deployed in 1 and 2 leaves all of the native 5′-nucleotide molecular recognition Sites intact while it restricts the framework to a low-energy anti glycosyl conformation and an extended phosphate disposition. This provides a spatial presence that approximates nearly three-quarters of the protein-bound 5′-nucleotide ligands described in the Protein Data Bank. The tether has a low structural and electronic impact, occupies a region of space (over the β-face of the furan ring) seldom penetrated by proteins, and should be accommodated as readily on purine-based 5′-nucleotide frameworks as on pyrimidine-based ones. Because of its unique and attractive features, this new motif for the conformational restriction of 5′-nucleotides is expected to be useful for producing probes of structure/function relationships and in assessing the conformational binding requirements that enzymes and receptor sites have for their natural 5′-nucleotide-based ligands.
- Groziak, Michael P.,Thomas, David W.
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- 2'(3')-O-BENZOYLURIDINE 5' LINKED TO GLASS: AN ALL-PURPOSE SUPPORT FOR SOLID PHASE SYNTHESIS OF OLIGODEOXYRIBONUCLEOTIDES
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Porous glass containing 2'(3')-O-benzoyluridine 5'-succinyl ligands serves as a universal support for construction of oligodeoxyribonucleotides of any sequence, using either the phosphotriester or the phosphite approach.At the conclusion of a synthesis, t
- Gough, G.R.,Brunden, M.J.,Gilham, P.T.
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- NOVEL COMPOUNDS AS ANTI-MYCOBACTERIALS
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The present disclosure relates to antibacterial compounds. In particular, the compounds are for inhibiting the growth of bacteria, particularly Mycobacterium tuberculosis (Mtb), and/or targeting bacteria having phospho-MurNAc-pentapeptidetranslocase. The present disclosure also relates to compositions containing these compounds and methods of the use of these compounds and compositions.
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Page/Page column 55; 56
(2018/07/05)
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- Linkers and co-coupling agents for optimization of oligonucleotide synthesis and purification on solid supports
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A method of modulation of synthesis capacity on and cleavage properties of synthetic oligomers from solid support is described. The method utilizes linker molecules attached to a solid surface and co-coupling agents that have similar reactivities to the coupling compounds with the surface functional groups. The preferred linker molecules provide an increased density of polymers and more resistance to cleavage from the support surface. The method is particularly useful for synthesis of oligonucleotides, oligonucleotides microarrays, peptides, and peptide microarrays. The stable linkers are also coupled to anchor molecules for synthesis of DNA oligonucleotides using on support purification, eliminating time-consuming chromatography and metal cation presence. Oligonucleotides thus obtained can be directly used for mass analysis, DNA amplification and ligation, hybridization, and many other applications.
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- Straightforward synthesis of 3'-deoxy-3',4'-didehydronucleoside-5'- aldehydes via 2',3'-O-orthoester group elimination: A simple route to 3',4'-didehydronucleosides
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Straightforward, high-yielding syntheses of 3'-deoxy-3',4'- didehydronucleoside-5'-aldehydes and 3'-deoxy-3',4'-didehydronucleosides starting from 2',3'-O-orthoester derivatives of ribonucleosides are described.
- Petrová, Magdalena,Budě?ínsky, Milo?,Rosenberg, Ivan
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supporting information; experimental part
p. 6874 - 6876
(2011/03/18)
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- Synthesis of selenium- and tellurium-containing nucleosides derived from uridine
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The synthesis of selenium- and tellurium-containing nucleosides, derived from uridine is described herein. These compounds were prepared in a concise and short synthetic route in good yields, by nucleophilic substitution of a tosylate group by organoselen
- Braga, Antonio L.,Severo Filho, Wolmar A.,Schwab, Ricardo S.,Rodrigues, Oscar E.D.,Dornelles, Luciano,Braga, Hugo C.,Lüdtke, Diogo S.
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body text
p. 3005 - 3007
(2009/09/28)
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- Dinucleoside poly(borano)phosphate derivatives and uses thereof
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Dinucleoside poly(borano)phosphates are provided that can be useful for prevention or treatment of diseases or disorders modulated by P2Y receptors such as type 2 diabetes, cystic fibtosis and cancer.
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Page/Page column 11
(2010/11/25)
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- Process for purifying 2',3'-dideoxynucleosides
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A biological process for producing a 2',3'-dideoxynucleoside from 2',3'-dideoxyuridine is disclosed. the 2',3'-dideoxynucleoside can be purified readily using a porous nonpolar resin adsorbent.
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- Synthesis of Nucleotide 5'-Diphosphates from 5'-O-Tosyl Nucleosides
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Procedures are described for the synthesis of nucleoside 5'-diphosphates, methanediphosphonates, and difluoromethanediphosphonates.The general strategy involves protection of the nucleosides as amidine, 2',3'-methoxymethylidene, and 3'-(tert-butyldimethylsilyl) derivatives prior to tosylation with tosyl chloride and (N,N-dimethylamino)pyridine.Deprotection, followed by displacement of the tosyl moiety with the tris(tetra-n-butylammonium) pyrophosphate, methanediphosphonate, or difluoromethanediphosphonate salts gave the desired products.The ammonium salts of the nucleotides were purified by flash chromatography on cellulose or medium pressure ion-exchange chromatography on DEAE Fractogel.Syntheses are reported for UDP (18), CDP (19), TDP (20), GDP (21), ADP (23), 2',3'-isopropylidene-ADP (22), adenosine 5'-methanediphosphonate (24), adenosine 5'-difluoromethanediphosphonate (25), and deoxyadenosine 5'-methanediphosphonate (27).In addition ATP (26) was prepared by treatment of 5'-O-tosyladenosine with tetrakis(tetra-n-butylammonium) thiophosphate.Yields for the displacement reactions ranged from 43percent to 93percent.
- Davisson, V. Jo,Davis, Darrell R.,Dixit, Vyas M.,Poulter, C. Dale
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p. 1794 - 1801
(2007/10/02)
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