130945-04-9Relevant articles and documents
Synthesis of DNAs with succinamide internucleoside linkages and its application in discrimination of T-C mismatch
Sun, Yawei,Lü, Huanfang,Sun, Limei,Wang, Dong,Wang, Jiqian
, (2021)
Peptide nucleic acid (PNA) has many applications in molecular biology and biotechnology, and research continues on modifying the PNA backbone to improve its functionality. We synthesized PNA in our case, artificial DNA that contains neutral succimamide as internucleoside linkages and applied it to mismatch recognition. We embedded the succinamide linkages into DNA by incorporating thymidine–succinamide–thymidine (TST) phosphoramidite at specific sites via standard DNA synthesis. Ultraviolet spectroscopy and melting temperature experiments suggested that such mixed-backbone DNA forms a B-type duplex with natural DNA. We observed a 20 kJ/mol decrease in enthalpy when we incorporated a succinamide linkage into a DNA–PNA duplex. We examined mismatch recognition of the mixed-backbone DNA, and observed that TST embedded DNA recognizes T-C mismatches.
Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine
Korvinson, Kirill A.,Akula, Hari K.,Malinchak, Casina T.,Sebastian, Dellamol,Wei, Wei,Khandaker, Tashrique A.,Andrzejewska, Magdalena R.,Zajc, Barbara,Lakshman, Mahesh K.
supporting information, p. 166 - 176 (2020/01/02)
Facile reduction of aryl halides with a combination of 5% Pd/C, B2(OH)4, and 4-methylmorpholine is reported. Aryl bromides, iodides, and chlorides were efficiently reduced. Aryl dihalides containing two different halogen atoms underwent selective reduction: I over Br and Cl, and Br over Cl. Beyond these, aryl triflates were efficiently reduced. This combination was broadly general, effectuating reductions of benzylic halides and ethers, alkenes, alkynes, aldehydes, and azides, as well as for N-Cbz deprotection. A cyano group was unaffected, but a nitro group and a ketone underwent reduction to a low extent. When B2(OD)4 was used for aryl halide reduction, a significant amount of deuteriation occurred. However, H atom incorporation competed and increased in slower reactions. 4-Methylmorpholine was identified as a possible source of H atoms in this, but a combination of only 4-methylmorpholine and Pd/C did not result in reduction. Hydrogen gas has been observed to form with this reagent combination. Experiments aimed at understanding the chemistry led to the proposal of a plausible mechanism and to the identification of N,N-bis(methyl-d3)pyridin-4-amine (DMAP-d6) and B2(OD)4 as an effective combination for full aromatic deuteriation. (Figure presented.).
OLIGONUCLEOTIDE COMPOSITIONS AND METHODS OF MAKING THE SAME
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Paragraph 00488; 00505-00512, (2015/11/24)
The present disclosure provides a solid phase method of making oligonucleotides via sequential coupling cycles including at least one coupling of a dinucleotide dimer subunit to a free 3'-terminal group of a growing chain. The oligonucleotides include at least two nucleoside subunits joined by a N3'→P5' phosphoramidate linkage. The method may include the steps of (a) deprotecting the protected 3' amino group of a terminal nucleoside attached to a solid phase support, said deprotecting forming a free 3' amino group; (b) contacting the free 3' amino group with a 3'-protected amino-dinucleotide-5'-phosphoramidite dimer in the presence of a nucleophilic catalyst to form an internucleoside N3'→P5' phosphoramidite linkage; and (c) oxidizing (e.g., sulfurizing) the linkage. The compositions produced by the subject methods may include a reduced amount of one or more (N-x) oligonucleotide products. Also provided are pharmaceutical compositions including the subject oligonucleotide compositions.
5′-silylated 3′-1,2,3-triazolyl thymidine analogues as inhibitors of West Nile Virus and Dengue virus
Vernekar, Sanjeev Kumar V.,Qiu, Li,Zhang, Jing,Kankanala, Jayakanth,Li, Hongmin,Geraghty, Robert J.,Wang, Zhengqiang
, p. 4016 - 4028 (2015/05/27)
West Nile virus (WNV) and Dengue virus (DENV) are important human pathogens for which there are presently no vaccine or specific antivirals. We report herein a 5′-silylated nucleoside scaffold derived from 3′-azidothymidine (AZT) consistently and selectively inhibiting WNV and DENV at low micromolar concentrations. Further synthesis of various triazole bioisosteres demonstrated clear structure-activity relationships (SARs) in which the antiviral activity against WNV and DENV hinges largely on both the 5′-silyl group and the substituent of 3′-triazole or its bioisosteres. Particularly interesting is the 5′ silyl group which turns on the antiviral activity against WNV and DENV while abrogating the previously reported antiviral potency against human immunodeficiency virus (HIV-1). The antiviral activity was confirmed through a plaque assay where viral titer reduction was observed in the presence of selected compounds. Molecular modeling and competitive S-adenosyl-l-methionine (SAM) binding assay suggest that these compounds likely confer antiviral activity via binding to methyltransferase (MTase).
Synthesis of all four nucleoside-based β-amino acids as protected precursors for the synthesis of polyamide-DNA with alternating α-amino acid and nucleoside-β-amino acids
Bagmare, Seema,Varada, Manojkumar,Banerjee, Anjan,Kumar, Vaijayanti A.
, p. 1210 - 1216 (2013/02/23)
A simple approach is described for the synthesis of all four orthogonally protected nucleoside-β-amino acids from commercially available starting materials. Synthesis of a model tetrameric DNA sequence in 5′-3'direction employing trityl strategy and glycine as α-amino acid alternating with nucleoside-β amino acids is described.
Oligonucleotide analogues containing a C3′-NH-C(O)-CH 2-C5′ amide internucleotide bond
Varizhuk,Kochetkova,Kolganova,Timofeev,Florent'ev
, p. 199 - 206 (2011/09/19)
A dinucleotide containing a C3′-NH-C(O)-CH2-C5′ amide internucleotide bond was synthesized by the interaction of 3′-deoxy-3′-amino-5′-O-(tert-butyldimethylsilyl)thymidine with 3′-O-benzyl-2′-O-tert-butyldimethylsilyl-5′-deoxy-5′- carboxymethylr
N3′→P5′ Oligodeoxyribonucleotide Phosphoramidates: A New Method of Synthesis Based on a Phosphoramidite Amine-Exchange Reaction
Nelson, Jeffrey S.,Fearon, Karen L.,Nguyen, Mark Q.,McCurdy, Sarah N.,Frediani, Jeff E.,Foy, Michael F.,Hirschbein, Bernard L.
, p. 7278 - 7287 (2007/10/03)
A new method for the synthesis of N3′→P5′ phosphoramidate oligodeoxynucleotides is demonstrated. Described herein is the synthesis of the monomers utilized in the phosphoramidite amine-exchange process and the experimental details pertaining to this new mode of chain assembly. The phosphoramidite amine-exchange method generates coupling yields in the 92-95% range per cycle and further enables the synthesis of chimeric phosphoramidate/phosphodiester or phosphoramidate/ phosphorothioate oligonucleotides with no instrument modifications.
