- Concurrent Prebiotic Formation of Nucleoside-Amidophosphates and Nucleoside-Triphosphates Potentiates Transition from Abiotic to Biotic Polymerization
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Polymerization of nucleic acids in biology utilizes 5′-nucleoside triphosphates (NTPs) as substrates. The prebiotic availability of NTPs has been unresolved and other derivatives of nucleoside-monophosphates (NMPs) have been studied. However, this latter approach necessitates a change in chemistries when transitioning to biology. Herein we show that diamidophosphate (DAP), in a one-pot amidophosphorylation-hydrolysis setting converts NMPs into the corresponding NTPs via 5′-nucleoside amidophosphates (NaPs). The resulting crude mixture of NTPs are accepted by proteinaceous- and ribozyme-polymerases as substrates for nucleic acid polymerization. This phosphorylation also operates at the level of oligonucleotides enabling ribozyme-mediated ligation. This one-pot protocol for simultaneous generation of NaPs and NTPs suggests that the transition from prebiotic-phosphorylation and oligomerization to an enzymatic processive-polymerization can be more continuous than previously anticipated.
- Arriola, Joshua T.,Jiménez, Eddy I.,Krishnamurthy, Ramanarayanan,Lin, Huacan,Müller, Ulrich F.
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- Supported Synthesis of Adenosine Nucleotides and Derivatives on a Benzene-Centered Tripodal Soluble Support
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The first soluble-phase synthesis of adenosine nucleotides including α,β and β,γ-methylene bisphosphonate analogues on a multi-pod support is reported. Anchoring of a 2’,3’-protected purine nucleoside to the tripodal support via the nucleobase was successfully achieved using a microwave assisted Cu(I)-catalyzed azide-alkyne cycloaddition. Then, phosphorylation was performed, followed by cleavage with aqueous ammonia to provide adenine derivatives, and finally deprotection. When using benzylamine instead of ammonia, a derivative with N6-benzylamine adenine as nucleobase was obtained. This methodology allows to access adenosine 5’-mono, di and triphosphates, as well as various analogues of pharmacological interest in modest to good yields.
- Appy, Lucie,Peyrottes, Suzanne,Roy, Béatrice
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- A Modular Synthesis of Modified Phosphoanhydrides
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Phosphoanhydrides (P-anhydrides) are ubiquitously occurring modifications in nature. Nucleotides and their conjugates, for example, are among the most important building blocks and signaling molecules in cell biology. To study and manipulate their biological functions, a diverse range of analogues have been developed. Phosphate-modified analogues have been successfully applied to study proteins that depend on these abundant cellular building blocks, but very often both the preparation and purification of these molecules are challenging. This study discloses a general access to P-anhydrides, including different nucleotide probes, that greatly facilitates their preparation and isolation. The convenient and scalable synthesis of, for example, 18O labeled nucleoside triphosphates holds promise for future applications in phosphoproteomics. Building the building blocks: This study discloses a general method for the functionalization of unprotected nucleotides and sugar phosphates with P-amidites in a highly modular way. The strategy facilitates the preparation of thiophosphate-containing nucleotides, 18O-labeled nucleoside triphosphates, and farnesylated nucleotides, as well as a range of dinucleoside polyphosphates and nucleotide sugars.
- Hofer, Alexandre,Cremosnik, Gregor S.,Müller, Andr C.,Giambruno, Roberto,Trefzer, Claudia,Superti-Furga, Giulio,Bennett, Keiryn L.,Jessen, Henning J.
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supporting information
p. 10116 - 10122
(2015/07/07)
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- A procedure for the preparation and isolation of nucleoside-5′-diphosphates
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Tris[bis(triphenylphosphoranylidene)ammonium] pyrophosphate (PPN pyrophosphate) was used in the SN2 displacements of the tosylate ion from 5′-tosylnucleosides to afford nucleoside-5′-diphosphates. Selective precipitation permitted the direct isolation of nucleoside-5′-diphosphates from crude reaction mixtures.
- Korhonen, Heidi J.,Bolt, Hannah L.,Hodgson, David R. W.
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p. 469 - 472
(2015/06/08)
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- A P(V)-N activation strategy for the synthesis of nucleoside polyphosphates
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A general and high-yielding synthesis of nucleoside 5′-triphosphates (NTPs) and nucleoside 5′-diphosphates (NDPs) from protected nucleoside 5′-phosphoropiperidates promoted by 4,5-dicyanoimidazole (DCI) has been developed. 31P NMR tracing experiments showed that the sequential deprotection and coupling reactions were exceptionally clean. The phosphoropiperidate exhibited superior reactivity to the conventional phosphoromorpholidate toward DCI-promoted NTP/NDP synthesis. The experimental results suggested that the mechanism of DCI activation could be distinctive for NTP and NDP synthesis, depending on the different nucleophilicity of pyrophosphate and phosphate.
- Sun, Qi,Gong, Shanshan,Sun, Jian,Liu, Si,Xiao, Qiang,Pu, Shouzhi
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p. 8417 - 8426
(2013/09/24)
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- A Novel Synthesis of Nucleoside 5'-Triphosphates
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Facile syntheses of ribonucleoside 5'-triphosphates have been accomplished in good yield (>60percent) in a one-pot reaction of unprotected nucleosides with phosphoryl chloride followed by treatment of the resulting phosphorodichloridate with tri-n-butylammonium phosphate in the presence of dimethylformamide.
- Mishra, Nrusingha C.,Broom, Arthur D.
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p. 1276 - 1277
(2007/10/02)
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- Multiple molecular recognition and catalysis. A multifunctional anion receptor bearing an anion binding site, an intercalating group, and a catalytic site for nucleotide binding and hydrolysis
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The multifunctional receptor molecule 2 has been designed and synthesized in order to achieve higher molecular recognition and reaction selectivity via multiple interactions with bound substrates. It combines three functional subunits: two recognition sites - a macrocyclic polyammonium moiety as anion binding site and an acridine side-chain for stacking interactions - as well as a catalytic amino group in the macrocycle for facilitating hydrolytic reactions. Compound 2 binds mono- and dinucleotide polyphosphates by simultaneous interactions between its macrocyclic polycationic moiety and the polyphosphate chain as demonstrated by 31P NMR spectroscopy and by stacking between its acridine derivative and the nucleic base of nucleotides as observed by both 1H NMR spectroscopy and by fluorescence spectrophotometry. Binding of nucleotides by protonated 2 induces significant upfield shifts of the polyphosphate signals and of protons of the acridine moiety of 2 as well as of the adenine and the anomeric proton of the nucleotides; at the same time the proton signals corresponding to CH2 groups of the macrocyclic part of 2 are downfield shifted. Upon complexation of ATP and CTP, the fluorescence emission of 2 is enhanced, whereas guanosine triphosphate causes a slight quenching; thus, 2 acts as a sensitive and selective fluorescent probe for ATP. At neutral pH the hydrolytic reaction proceeds, at least in part, through a covalent intermediate, the phosphorylated macrocycle 2 indicating nucleophilic catalysis. Compound 2 shows greater selectivity between ATP and ADP than the parent compound 1 which does not contain the acridine binding site. 2 also binds strongly to DNA plasmid pBR 322 at 10-6 M probably via a double type of interaction, involving both intercalation and electrostatic interactions with the phosphate groups.
- Hosseini, Mir Wais,Blacker, A. John,Lehn, Jean-Marie
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p. 3896 - 3904
(2007/10/02)
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