80971-33-1Relevant academic research and scientific papers
Silylation of 5'-O-DMT-2'-deoxynucleosides using dibenzo [18] crown-6-and PTC
Kore,Patil,Salunkhe
, p. 2599 - 2603 (1993)
3'-O-silylated derivatives of 5'-O-DMT-2'-deoxynucleoside (2) were synthesized in high yield by reaction of 5'-O-DMT-2'-deoxynucleosides (1) with tert-butyl dimethylsilylchloride using sodium hydride, benzyltriethylammonium chloride [TEBA] and a catalytic
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
, (2020/11/12)
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.
Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides
Baran, Phil S.,Eastgate, Martin D.,Knouse, Kyle W.,Padial, Natalia M.,Rivas-Bascón, Nazaret,Schmidt, Michael A.,Vantourout, Julien C.,Xu, Dongmin,Zheng, Bin
supporting information, (2020/03/30)
Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required - the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.
Synthesis of stable azide and alkyne functionalized phosphoramidite nucleosides
Lingala, Suresh,Nordstr?m, Lars Ulrik,Mallikaratchy, Prabodhika R.
supporting information, p. 211 - 213 (2019/01/04)
The use of CuAAC chemistry to crosslink and stabilize oligonucleotides has been limited by the incompatibility of azides with the phosphoramidites used in automated oligonucleotide synthesis. Herein we report optimized reaction conditions to synthesize azide derivatives of thymidine and cytidine phosphoramidites. Investigation of the stability of the novel phosphoramidites using 31P NMR at room temperature showed less than 10% degradation after 6 h. The azide modified thymidine was successfully utilized as an internal modifier in the standard phosphoramidite synthesis of a DNA sequence. The synthesized azide and alkyne derivatives of pyrimidines will allow efficient incorporation of azide and alkyne click pairs into nucleic acids, thus widening the applicability of click chemistry in investigating the chemistry of nucleic acids.
REACTIVE, LIPOPHILIC NUCLEOSIDE BUILDING BLOCKS FOR THE SYNTHESIS OF HYDROPHOBIC NUCLEIC ACIDS
-
Paragraph 0453, (2019/06/20)
The present invention relates to a method for the isolation and/or identification of known or unknown sequences of nucleic acids (target sequences) optionally marked with reporter groups by base specific hybridation with complementary sequences using nucleolipids. The nucleolipids are prepared by lipophilizing nucleosides of formula (Ia) wherein Q represents a group having a substituted tetrahydrofuran ring and Bas represents a group having one or more heterocyclic rings having one or more heterocyclic nitrogen atoms.
A hydroxamic-acid-containing nucleoside inhibits DNA repair nuclease SNM1A
Doherty, William,Dürr, Eva-Maria,Baddock, Hannah T.,Lee, Sook Y.,McHugh, Peter J.,Brown, Tom,Senge, Mathias O.,Scanlan, Eoin M.,McGouran, Joanna F.
supporting information, p. 8094 - 8105 (2019/09/19)
Nine modified nucleosides, incorporating zinc-binding pharmacophores, have been synthesised and evaluated as inhibitors of the DNA repair nuclease SNM1A. The series included oxyamides, hydroxamic acids, hydroxamates, a hydrazide, a squarate ester and a squaramide. A hydroxamic acid-derived nucleoside inhibited the enzyme, offering a novel approach for potential therapeutic development through the use of rationally designed nucleoside derived inhibitors.
Correction to: Oxidative substitution of boranephosphonate diesters as a route to post-synthetically modified DNA (Journal of the American Chemical Society (2015) 137 (3253-3264) DOI: 10.1021/ja511145h)
-
supporting information, p. 13586 - 13586 (2017/10/06)
Supporting Information. In Figure S19, the LC-MS profile for ODN 15 as obtained from 37 scans has been added as part B. The ESI scans shown in parts A and B were obtained from the same sample. These ESI scans (16 and 37, respectively) generate essentially the same results. In Figure S21, the LC-MS profile for ODN 17 as obtained from 34 scans has been added as part B. The ESI scans as shown in parts A and B were obtained from the same sample. These ESI scans (78 and 37, respectively) generate essentially the same conclusions. As expected with more scans, several additional minor side products/impurities were observed with the profile from 78 scans as published. These LC-MS profiles were obtained from unpurified reaction mixtures as obtained from the controlled pore glass supports following synthesis. The quality of these products should be compared to the results obtained when the same crude reaction mixtures were analyzed by denaturing polyacrylamide gel electrophoresis (see Figure 2 in the original article). These additions do not alter any of the results or conclusions as presented in original publication.
COMPOUNDS COMPOSITIONS AND METHODS INCLUDING THERMALLY LABILE MOIETIES
-
Page/Page column 115; 116; 117, (2015/11/24)
The present invention generally relates to compounds that include one or more thermally labile protecting groups, compositions including the compounds, methods of making the compounds and compositions and methods of using the compounds and compositions. I
Intermolecular 'cross-torque': The N4-cytosine propargyl residue is rotated to the 'CH'-edge as a result of Watson-Crick interaction
Domingo, Olwen,Hellmuth, Isabell,J?schke, Andres,Kreutz, Christoph,Helm, Mark
, p. 5275 - 5283 (2015/07/15)
Propargyl groups are attractive functional groups for labeling purposes, as they allow CuAAC-mediated bioconjugation. Their size minimally exceeds that of a methyl group, the latter being frequent in natural nucleotide modifications. To understand under which circumstances propargyl-containing oligodeoxynucleotides preserve base pairing, we focused on the exocyclic amine of cytidine. Residues attached to the exocyclic N4 may orient away from or toward the Watson-Crick face, ensuing dramatic alteration of base pairing properties. ROESY-NMR experiments suggest a uniform orientation toward the Watson-Crick face of N4-propargyl residues in derivatives of both deoxycytidine and 5-methyl-deoxycytidine. In oligodeoxynucleotides, however, UV-melting indicated that N4-propargyl-deoxycytidine undergoes standard base pairing. This implies a rotation of the propargyl moiety toward the 'CH'-edge as a result of base pairing on the Watson-Crick face. In oligonucleotides containing the corresponding 5-methyl-deoxycytidine derivative, dramatically reduced melting temperatures indicate impaired Watson-Crick base pairing. This was attributed to a steric clash of the propargyl moiety with the 5-methyl group, which prevents back rotation to the 'CH'-edge, consequently preventing Watson-Crick geometry. Our results emphasize the tendency of an opposing nucleic acid strand to mechanically rotate single N4-substituents to make way for Watson-Crick base pairing, providing no steric hindrance is present on the 'CH'-edge.
Oxidative substitution of boranephosphonate diesters as a route to post-synthetically modified DNA
Paul, Sibasish,Roy, Subhadeep,Monfregola, Luca,Shang, Shiying,Shoemaker, Richard,Caruthers, Marvin H.
supporting information, p. 3253 - 3264 (2015/03/30)
The introduction of modifications into oligonucleotides is important for a large number of applications in the nucleic acids field. However, the method of solid-phase DNA synthesis presents significant challenges for incorporating many useful modifications that are unstable to the conditions for preparing synthetic DNA. Here we report that boranephosphonate diesters undergo facile nucleophilic substitution in a stereospecific manner upon activation by iodine. We have subsequently used this reactivity to post-synthetically introduce modifications including azides and fluorophores into DNA by first synthesizing boranephosphonate-linked 2′-deoxyoligonucleotides and then treating these oligomers with iodine and various nucleophiles. In addition, we show that this reaction is an attractive method for preparing stereodefined phosphorus-modified oligonucleotides. We have also examined the mechanism of this reaction and show that it proceeds via an iodophosphate intermediate. Beyond nucleic acids synthesis, due to the ubiquity of phosphate derivatives in natural compounds and therapeutics, this stereospecific reaction has many potential applications in organophosphorus chemistry.
