84-21-9Relevant academic research and scientific papers
A Stark Contrast to Modern Earth: Phosphate Mineral Transformation and Nucleoside Phosphorylation in an Iron- and Cyanide-Rich Early Earth Scenario
Burcar, Bradley,Casta?eda, Alma,Lago, Jennifer,Daniel, Mischael,Pasek, Matthew A.,Hud, Nicholas V.,Orlando, Thomas M.,Menor-Salván, César
, p. 16981 - 16987 (2019/11/11)
Organophosphates were likely an important class of prebiotic molecules. However, their presence on the early Earth is strongly debated because the low availability of phosphate, which is generally assumed to have been sequestered in insoluble calcium and iron minerals, is widely viewed as a major barrier to organophosphate generation. Herein, we demonstrate that cyanide (an essential prebiotic precursor) and urea-based solvents could promote nucleoside phosphorylation by transforming insoluble phosphate minerals in a “warm little pond” scenario into more soluble and reactive species. Our results suggest that cyanide and its derivatives (metal cyanide complexes, urea, ammonium formate, and formamide) were key reagents for the participation of phosphorus in chemical evolution. These results allow us to propose a holistic scenario in which an evaporitic environment could concentrate abiotically formed organics and transform the underlying minerals, allowing significant organic phosphorylation under plausible prebiotic conditions.
Natural occurrence of 2′,5′-linked heteronucleotides in marine sponges
Lopp, Annika,Reintamm, Tonu,Kuusksalu, Anne,Tammiste, Indrek,Pihlak, Arno,Kelve, Merike
experimental part, p. 235 - 254 (2010/10/19)
2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′p5′U, A2′p5′C, G2′p5′A and G2′p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.
An improved one-pot synthesis of nucleoside 5'-triphosphate analogues
Gillerman, Irina,Fischer, Bilha
, p. 245 - 256 (2011/08/06)
Nucleoside 5'-triphosphate (NTP) analogues are valuable tools for biochemical and medicinal research. Therefore, a facile and efficient synthesis of NTP analogues is required. Here, we report on an improved nucleoside 5'-triphosphorylation procedure to obtain pure products after liquid chromotagrpahy (LC) separation with no need for high performance liquid chromatography (HPLC) purification. To improve the selectivity of the reaction we attempted the optimization of several parameters such as solvent, pyrophosphate nucleophilicity, time and temperature of the reaction. Eventually, the reaction was optimized by decreasing the temperature to -15°C and increasing the reaction time to 2 hours, based on monitoring time-dependent product distribution using 31P NMR. Furthermore, the NTPs were obtained as pure products after LC separation, which was impossible in the original Ludwig procedure. Good yields were obtained for all studied natural and synthetic nucleosides.
Kinetic analysis of hydrolytic reaction of homo- and heterochiral adenylyl(3′-5′)adenosine isomers: Breaking homochirality reduces hydrolytic stability of RNA
Urata, Hidehito,Sasaki, Rie,Morita, Hiroyo,Kusumoto, Marina,Ogawa, Yoko,Mitsuda, Kozue,Akagi, Masao
, p. 2578 - 2580 (2007/10/03)
The hydrolytic stability of the diastereomeric isomers of ApA was compared and the results show that heterochiral ApAs are more rapidly hydrolyzed than homochiral ApAs at low temperatures, suggesting that hydrolytic selection in cold environments in conjunction with selective polymerization may have been effective in enriching the homochirality of RNA. The Royal Society of Chemistry 2005.
Dinuclear Zn2+ complexes in the hydrolysis of the phosphodiester linkage in a diribonucleoside monophosphate diester.
Yashiro, Morio,Kaneiwa, Hideki,Onaka, Kenichi,Komiyama, Makoto
, p. 605 - 610 (2007/10/03)
Dizinc complexes that were formed from 2:1 mixtures of Zn(NO3)2 and dinucleating ligands TPHP (1), TPmX (2) or TPpX (3) in aqueous solutions efficiently hydrolyzed diribonucleoside monophosphate diesters (NpN) under mild conditions. The dinucleating ligand affected the structure of the aquo-hydroxo-dizinc core, resulting in different characteristics in the catalytic activities towards NpN cleavage. The pH-rate profile of ApA cleavage in the presence of (Zn2+)(2)-1 was sigmoidal, whereas those of (Zn2+)(2)-2 and (Zn2+)(2)-3 were bell-shaped. The pH titration study indicated that (Zn2+)(2)-1 dissociates only one aquo proton (up to pH 12), whereas (Zn2+)(2)-2 dissociates three aquo protons (up to pH 10.7). The observed differences in the pH-rate profile are attributable to the various distributions of the monohydroxo-dizinc species, which are responsible for NpN cleavage. As compared to that using (Zn2+)(2)-1, the NpN cleavage using (Zn2+)(2)-2 showed a greater rate constant, with a higher product ratio of 3'-NMP/2'-NMP. The saturation behaviors of the rate, with regard to the concentration of NpN, were analyzed by Michaelis-Menten type kinetics. Although the binding of (Zn2+)(2)-2 to ApA was weaker than that of (Zn2+)(2)-1, (Zn2+)(2)-2 showed a greater kcat value than (Zn2+)(2)-1, resulting in higher ApA cleavage activity of the former.
Phosphodiester Cleavage of Ribonucleoside Monophosphates and Polyribonucleotides by Homo- and Heterodinuclear Metal Complexes of a Cyclohexane-Based Polyamino-Polyol Ligand
Jancso, Attila,Mikkola, Satu,Loennberg, Harri,Hegetschweiler, Kaspar,Gajda, Tamas
, p. 5404 - 5415 (2007/10/03)
The ability of the dinuclear complexes of tdci [1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol] to promote the cleavage of the phosphodiester bonds of nucleoside 2′,3′-cyclic monophosphates, dinucleoside monophosphates and polyribonucleotides has been studied. The homodinuclear copper(II) and zinc(II) complexes efficiently promote the hydrolysis of cyclic nucleotides. The second-order rate constant (k2≈0.44M-1S-1) estimated for the cleavage of 2′,3′-cAMP induced by dinuclear copper(II) complexes is about 107 times greater than that for the hydroxide-ion-catalysed reaction. The complex selectively cleaves the 2′O-P bond of 2′,3′-cUMP and forms the 3′-product in 91% yield. An equimolar mixture of copper(II), zinc(II) and tdci proved to be more efficient than either of the binary systems: a 7-20-fold rate enhancement was observed for the cleavage of 2′,3′-cNMP substrates. The half-life for the hydrolysis of 2′,3′-cAMP decreased from 300 days to five minutes at 25°C when the concentration of each of the three components was 2.5mM. In contrast to the copper(II) or zinc(II) complexes of tdci, the heterodinuclear species promoted the hydrolysis of several dinucleoside monophosphates. For two ApA isomers, cleavage of the 3′,5′-bond was about 6.5 times faster than cleavage of the 2′,5′-bond. On the basis of the kinetic data, a trifunctional mechanism is suggested for the heterodinuclear-complex-promoted cleavage of the phosphodiester bond. Double Lewis acid activation occurs when the metal ions bind to the phosphate oxygen atoms. In particular, a metal-bound hydroxide ion serves as a general base or a nucleophilic catalyst, and, presumably, a zinc(II)-bound aqua ligand behaves as a general acid and facilitates the departure of the leaving alkoxide group. The effect of the complexes on the hydrolysis of poly(U), poly(A) and type III native RNA was also investigated, and, for the first time, kinetic data on the cleavage of the phosphodiester bonds of polyribonucleotides by a dinuclear complex was obtained.
The pKa of the internucleotidic 2′-hydroxyl group in diribonucleoside (3′→5′) monophosphates
Acharya,Foeldesi,Chattopadhyaya
, p. 1906 - 1910 (2007/10/03)
Ionization of the internucleotidic 2′-hydroxyl group in RNA facilitates transesterification reactions in Group I and II introns (splicing), hammerhead and hairpin ribozymes, self-cleavage in lariatRNA, and leadzymes and tRNA processing by RNase P RNA, as well as in some RNA cleavage reactions promoted by ribonucleases. Earlier, the pKa of 2′-OH in mono- and diribonucleoside (3′-5′) monophosphates had been measured under various nonuniform conditions, which make their comparison difficult. This work overcomes this limitation by measuring the pKa values for internucleotidic 2′-OH of eight different diribonucleoside (3′-5′) monophosphates under a set of uniform noninvasive conditions by 1H NMR. Thus the pKa is 12.31 (±0.02) for ApG and 12.41 (±0.04) for ApA, 12.73 (±0.04) for GpG and 12.71 (±0.08) for GpA, 12.77 (±0.03) for CpG and 12.88 (±0.02) for CpA, and 12.76 (±0.03) for UpG and 12.70 (±0.03) for UpA. By comparing the pKas of the respective 2′-OH of monomeric nucleoside 3′-ethyl phosphates with that of internucleotidic 2′-OH in corresponding diribonucleoside (3′→5′) monophosphates, it has been confirmed that the aglycons have no significant effect on the pKa values of their 2′-OH under our measurement condition, except for the internucleotidic 2′-OH of 9-adeninyl nucleotide at the 5′-end (ApA and ApG), which is more acidic by 0.3-0.4 pKα units.
Modeling of prebiotic catalysis with adenylated polymeric templates: Crystal structure studies and kinetic characterization of template-assisted phosphate ester hydrolysis
Srivatsan,Parvez, Masood,Verma, Sandeep
, p. 5184 - 5191 (2007/10/03)
We have synthesized and characterized novel, copper-metalated, polymeric templates that contain adenine nucleobases. These promote hydrolysis of nonnatural and natural phosphate ester substrates in a highly efficient and catalytic fashion. The crystal structure of the copper-containing adenylated monomer reveals the formation of a polymeric array, through coordination to both N1 and N7 atoms. Possible implications of these studies for prebiotic catalysis, involving synergism between adenine and copper ions, are also discussed.
Effect of alkaline earth metal ions on the phosphodiester hydrolysis of RNA
Yashiro, Morio,Higuchi, Maiko,Washizu, Yusuke,Komiyama, Makoto
, p. 1843 - 1844 (2007/10/03)
Hydrolyses of di- and triribonucleotides assisted by alkaline earth metal ions were investigated at pH 7.3 and 50 °C. Mg2+ was the most effective for the phosphodiester hydrolysis, and the rate exhibited first-order dependence on the concentration of Mg2+ in a range of 0.1-1.0 mol dm-3.
