- Efficient and selective cleavage of RNA oligonucleotides by calix[4]arene-based synthetic metallonucleases
-
Di- and trinuclear copper(II) complexes of [12]aneN3 macrocycles anchored at the upper rim of cone calix[4]arenes in 1,2-, 1,3-, and 1,2,3-positions were investigated as cleaving agents of 6-, 7-, and 17-meric oligoribonucleotides. A kinetic investigation of the cleavage reactions was carried out using gel electrophoresis to separate and analyze reactants and products having a radioactive phosphate label in the terminal opposition. The degree of cooperation was assessed on the basis of a comparison with rates of cleavage by mononuclear controls. A remarkable selectivity of cleavage of the CpA phosphodiester bond was observed for all metal complexes, in sharp contrast with the UpU and UpG selectivity previously observed in the cleavage of diribonucleoside monophosphates by the same metal complexes. The highest rate acceleration, brought about in the cleavage of the 5′-pCpA bond in hexanucleotide 9 by 50 μM trinuclear complex 5-Cu3 (water solution, pH 7.4, 50°C), amounts to 5 × 105-fold, as based on the estimated background reactivity of the CpA dimer. Selectivity in the cleavage of oligoribonucleotides by copper(II) complexes closely resembles that experienced by ribonuclease A and by a number of metal-independent RNase A mimicks. The possible role of the dianionic phosphate at the 5′-terminal positions as a primary anchoring site for the metal catalyst is discussed.
- Cacciapaglia, Roberta,Casnati, Alessandro,Mandolini, Luigi,Peracchi, Alessio,Reinhoudt, David N.,Salvio, Riccardo,Sartori, Andrea,Ungaro, Rocco
-
-
Read Online
- A nucleotide dimer synthesis without protecting groups using montmorillonite as catalyst
-
A synthesis has been developed providing nucleotide dimers comprising natural or unnatural nucleoside residues. A ribonucleoside 5-phosphorimidazolide is added to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of protecting groups. Approximately 30% of the imidazolide is converted into each 2-5 dimer and 3-5 dimer with the rest hydrolyzed to the 5-monophosphate. Experiments with many combinations have suggested the limits to which this method may be applied, including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5-monophosphates.
- Joshi, Prakash C.,Aldersley, Michael F.,Zagorevskii, Dmitri V.,Ferris, James P.
-
p. 536 - 566
(2012/10/08)
-
- Synthesis and enzymatic deprotection of biodegradably protected dinucleoside-2′,5′-monophosphates: 3-(Acetyloxy)-2,2- bis(ethoxycarbonyl)propyl phosphoesters of 3′-O-(acyloxymethyl)adenylyl- 2′,5′-adenosines
-
As a first step towards a viable prodrug strategy for short oligoribonucleotides, such as 2-5A and its congeners, adenylyl-2′, 5′-adenosines bearing a 3-(acetyloxy)-2,2-bis(ethoxycarbonyl)propyl group at the phosphate moiety, and an (acetyloxy)methyl- or a (pivaloyloxy)methyl- protected 3′-OH group of the 2′-linked nucleoside have been prepared. The enzyme-triggered removal of these protecting groups by hog liver carboxyesterase at pH 7.5 and 37° has been studied. The (acetyloxy)methyl group turned out to be too labile for the 3′-O-protection, being removed faster than the phosphate-protecting group, which results in 2′,5′- to 3′,5′-isomerization of the internucleosidic phosphoester linkage. In addition, the starting material was unexpectedly converted to the 5′-O-acetylated derivative. (Pivaloyloxy)methyl group appears more appropriate for the purpose. The fully deprotected 2′,5′-ApA was accumulated as a main product, although, even in this case, the isomerization of the starting material takes place.
- Kiuru, Emilia,Ora, Mikko,Beigelman, Leonid,Blatt, Lawrence,Loennberg, Harri
-
experimental part
p. 266 - 286
(2011/10/05)
-
- Convenient Synthesis of Oligoribonucleotides Having 2'-5' and/or 3'-5' Phosphodiester Linkage
-
Sequence-defined oligoribonucleosides having 2'-5' and/or 3'-5' phosphodiester linkage have been synthesized by use of 5'-protected ribonucleoside 2',3'-cyclic phosphoramidite on solid support.In coupling reaction, pKa of azole as a catalyst governs the activation.The resulting 2'-5' and/or 3'-5' linked oligoribonucleotides were easily separated by reversed-phase chromatography.
- Ozaki, Hiroaki,Nakamoto, Akio,Shimidzu, Takeo
-
p. 959 - 962
(2007/10/02)
-
- THE RAPID CHEMICAL SYNTHESIS OF ARABINONUCLEOTIDES
-
A fast and convenient procedure for the chemical synthesis of arabinonucleotides which eliminates the multistep protection of the arabinonucleoside building blocks is described.Both solution and solid phase phosphite triester procedures are described.
- Damha, Masad J.,Usman, Nassim,Ogilvie, Kelvin K.
-
p. 1633 - 1636
(2007/10/02)
-
- Formation of Inter-nucleotide Bond: Use of p,p'-Dianisylphosphinyl as Protecting Group
-
A convenient method for the preparation of oligonucleotides using p,p'-dianisylphosphinyl as protecting group for 5'-OH of the ribose moiety of nucleosides is discribed.The dinucleotide, adenylyl-(5'-3')-adenosine has been prepared employing this reagent.
- Agrawal, Sudhir,Misra, Krishna
-
p. 687 - 688
(2007/10/02)
-
- The chemical synthesis of oligoribonucleotides. IX. A comparison of protecting groups in the dichloridite procedure
-
A series of phosphorodichloridites has been prepared incorporating the most commonly used phosphate protecting groups in oligonucleotide synthesis.The groups incude trichloroethyl, tribromoethyl, cyanoethyl, benzyl, methyl, p-chlorophenyl, and nitrophenetyl.The trichloroethyl and the nitrophenethyl appear to be the most stable groups while the cyanoethyl and methyl offer specific advantages.The benzyl and p-chlorophenyl groups are subject to limitations on their utility.Condensations can be carried out in a range of solvents incuding THF, pyridine, and DMF and at temperatures from -78 deg C to 20 deg C with a slight drop in yield with increasing temperature, at least for dinucleotide condensations.
- Ogilvie, Kelvin K.,Theriault, Nicole Y.,Seifert, Jan-Marcus,Pon, Richard T.,Nemer, Mona J.
-
p. 2686 - 2693
(2007/10/02)
-
- Formation of Inter-nucleotide Bond: Use of Diphenylphosphinothioyl Group as a Protective Group
-
A convenient method for the preparation of oligonucleotides using diphenylphosphinothioyl group as the protective group for 5'-OH of the ribose moiety of nucleoside is described.The dinucleotides, uridyl (5',3')-adenosine and adenylyl (5',3')-adenosine have been prepared employing this reagent.
- Agrawal, Sudhir,Misra, Krishna
-
p. 132 - 134
(2007/10/02)
-
