634-01-5Relevant academic research and scientific papers
Synthesis of adenosine cyclic 3′,5′ -phosphorofuoridate (camp-f)
Baraniak, Janina,Stec, Wojciech J.,Blackburn, G. Michael
, p. 8119 - 8122 (1995)
Work aimed at the chiral synthesis of both diastereomers of adenosine cyclic 3′,5′phosphorofluoridate, cAMP-F 7, is described. Attempted debenzoylation of the intermediate N6,N6,O2′tribenzoyladenosine cyclic 3′,5′-phosphorofluoridate 4 by ammonolysis resulted in cleavage of the P-F bond. Reaction of [Sp]-S-methyl adenosine 3′,5′-cyclophosphorothioate 6 with AgF gives a mixture of the two diastereoisomers of the cyclic phosphore fluoridate 7 along with adenosine 2′ ,3′-cyclic phosphate 8. The conversion of 7 into 8 can be completed under remarkably mild conditions. Possible mechanisms for this unusual transformation are discussed.
Cyanamide as a prebiotic phosphate activating agent-catalysis by simple 2-oxoacid salts
Tsanakopoulou, Maria,Sutherland, John D.
, p. 11893 - 11896 (2017)
Cyanamide is a prebiotically plausible compound that has previously been invoked as a phosphate activating agent. However, its reactions with phosphate monoesters are very slow and tend to be low yielding. We now report a fast and efficient phosphate activation reaction using cyanamide in the presence of glyoxylate or pyruvate. These simple 2-oxoacid salts are shown to function as catalysts and in an optimised system, adenosine-3′-phosphate was converted to adenosine-2′,3′-cyclic phosphate in 95% yield.
The Stereochemical Course of Substitution of Sulfur by Oxygen Nucleophiles in Five-membered Cyclic Phosphorothioates
Lowe, Gordon,Thelin, Mats
, p. 1947 - 1948 (1994)
The replacement of non-bridging sulfur in five-membered cyclic phosphorothioates by oxygen nucleophiles in the presence of bromine occurs with retention of configuration and has allowed the 31P NMR signals of the diastereoisomeric tert-butyldiphenyl silyl esters of 2',3'-cyclic adenosine monophosphate to be assigned.
Prebiotically Plausible RNA Activation Compatible with Ribozyme-Catalyzed Ligation
Song, Emilie Yeonwha,Jiménez, Eddy Ivanhoe,Lin, Huacan,Le Vay, Kristian,Krishnamurthy, Ramanarayanan,Mutschler, Hannes
supporting information, p. 2952 - 2957 (2020/12/13)
RNA-catalyzed RNA ligation is widely believed to be a key reaction for primordial biology. However, since typical chemical routes towards activating RNA substrates are incompatible with ribozyme catalysis, it remains unclear how prebiotic systems generated and sustained pools of activated building blocks needed to form increasingly larger and complex RNA. Herein, we demonstrate in situ activation of RNA substrates under reaction conditions amenable to catalysis by the hairpin ribozyme. We found that diamidophosphate (DAP) and imidazole drive the formation of 2′,3′-cyclic phosphate RNA mono- and oligonucleotides from monophosphorylated precursors in frozen water-ice. This long-lived activation enables iterative enzymatic assembly of long RNAs. Our results provide a plausible scenario for the generation of higher-energy substrates required to fuel ribozyme-catalyzed RNA synthesis in the absence of a highly evolved metabolism.
Harnessing chemical energy for the activation and joining of prebiotic building blocks
Liu, Ziwei,Wu, Long-Fei,Xu, Jianfeng,Bonfio, Claudia,Russell, David A.,Sutherland, John D.
, p. 1023 - 1028 (2020/10/26)
Life is an out-of-equilibrium system sustained by a continuous supply of energy. In extant biology, the generation of the primary energy currency, adenosine 5′-triphosphate and its use in the synthesis of biomolecules require enzymes. Before their emergence, alternative energy sources, perhaps assisted by simple catalysts, must have mediated the activation of carboxylates and phosphates for condensation reactions. Here, we show that the chemical energy inherent to isonitriles can be harnessed to activate nucleoside phosphates and carboxylic acids through catalysis by acid and 4,5-dicyanoimidazole under mild aqueous conditions. Simultaneous activation of carboxylates and phosphates provides multiple pathways for the generation of reactive intermediates, including mixed carboxylic acid–phosphoric acid anhydrides, for the synthesis of peptidyl–RNAs, peptides, RNA oligomers and primordial phospholipids. Our results indicate that unified prebiotic activation chemistry could have enabled the joining of building blocks in aqueous solution from a common pool and enabled the progression of a system towards higher complexity, foreshadowing today’s encapsulated peptide–nucleic acid system. [Figure not available: see fulltext.].
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.
Cleavage of short oligoribonucleotides by a Zn2+binding multi-nucleating azacrown conjugate
Laine, Maarit,L?nnberg, Tuomas,Helkearo, Mia,L?nnberg, Harri
, p. 111 - 117 (2016/10/04)
A multi-nucleating azacrown conjugate (5a) consisting of two 3,5-bis(1,5,9-triazacyclododecan-3-yloxymethyl)benzyl groups attached to 1 and 7 sites of cyclen was prepared and tested as an artificial ribonuclease. The conjugate in the presence of five equivalents of zinc nitrate expectedly showed uridine selectivity comparable to that 1,3,5-tris(1,5,9-triazacyclododecan-3-yl)benzene (2), a compound known to bind to two adjacent uridine residues and cleave the intervening phosphodiester bond. 5a was, however, unable to discriminate between two and three adjacent uridine residues, but cleaved oligonucleotides containing a UpU and UpUpU site at a comparable rate, even when present at sub-saturating concentrations.
Catalysis of diribonucleoside monophosphate cleavage by water soluble copper(II) complexes of calix[4]arene based nitrogen ligands
Cacciapaglia, Roberta,Casnati, Alessandro,Mandolini, Luigi,Reinhoudt, David N.,Salvio, Riccardo,Sartori, Andrea,Ungaro, Rocco
, p. 12322 - 12330 (2007/10/03)
Calix[4]arenes functionalized at the 1,2-, 1,3-, and 1,2,3-positions of the upper rim with [12]ane-N3 ligating units were synthesized, and their bi- and trimetallic zinc(II) and copper(II) complexes were investigated as catalysts in the cleavage of phosphodiesters as RNA models. The results of comparative kinetic studies using monometallic controls indicate that the subunits of all of the zinc(II) complexes and of the 1,3-distal bimetallic copper(II) complex 7-Cu2 act as essentially independent monometallic catalysts. The lack of cooperation between metal ions in the above complexes is in marked contrast with the behavior of the 1,2-vicinal bimetallic copper(II) complex 6-Cu2, which exhibits high catalytic efficiency and high levels of cooperation between metal ions in the cleavage of HPNP and of diribonucleoside monophosphates NpN′. A third ligated metal ion at the upper rim does not enhance the catalytic efficiency, which excludes the simultaneous cooperation in the catalysis of the three metal ions in 8-Cu 3. Rate accelerations relative to the background brought about by 6-Cu2 and 8-Cu3 (1.0 mM catalyst, water solution, pH 7.0, 50 °C) are on the order of 104-fold, largely independent of the nucleobase structure, with the exception of the cleavage of diribonucleoside monophosphates in which the nucleobase N is uracil, namely UpU and UpG, for which rate enhancements rise to 105-fold. The rationale for the observed selectivity is discussed in terms of deprotonation of the uracil moiety under the reaction conditions and complexation of the resulting anion with one of the copper(II) centers.
Simultaneous interaction with base and phosphate moieties modulates the phosphodiester cleavage of dinucleoside 3′,5′-monophosphates by dinuclear Zn2+complexes of Di(azacrown) ligands
Wang, Qi,Loennberg, Harri
, p. 10716 - 10728 (2007/10/03)
Five dinucleating ligands (1-5) and one trinucleating ligand (6) incorporating 1,5,9-triazacyclododecan-3-yloxy groups attached to an aromatic scaffold have been synthesized. The ability of the Zn2+ complexes of these ligands to promote the transesterification of dinucleoside 3′,5′-monophosphates to a 2′,3′-cyclic phosphate derived from the 3′-linked nucleoside by release of the 5′-linked nucleoside has been studied over a narrow pH range, from pH 5.8 to 7.2, at 90 °C. The dinuclear complexes show marked base moiety selectivity. Among the four dinucleotide 3′,5′-phosphates studied, viz. adenylyl-3′,5′-adenosine (ApA), adenylyl-3′,5′-uridine (ApU), uridylyl-3′,5′-adenosine (UpA), and uridylyl-3′, 5′-uridine (UpU), the dimers containing one uracil base (ApU and UpA) are cleaved up to 2 orders of magnitude more readily than those containing either two uracil bases (UpU) or two adenine bases (ApA). The trinuclear complex (6), however, cleaves UpU as readily as ApU and UpA, while the cleavage of ApA remains slow. UV spectrophotometric and 1H NMR spectroscopic studies with one of the dinucleating ligands (3) verify binding to the bases of UpU and ApU at less than millimolar concentrations, while no interaction with the base moieties of ApA is observed. With ApU and UpA, one of the Zn2+- azacrown moieties in all likelihood anchors the cleaving agent to the uracil base of the substrate, while the other azacrown moiety serves as a catalyst for the phosphodiester transesterification. With UpU, two azacrown moieties are engaged in the base moiety binding. The catalytic activity is, hence, lost, but it can be restored by addition of a third azacrown group on the cleaving agent.
Expeditious, potentially primordial, aminoacylation of nucleotides
Biron, Jean-Philippe,Parkes, Alastair L.,Pascal, Robert,Sutherland, John D.
, p. 6731 - 6734 (2007/10/03)
(Chemical Equation Presented) In the beginning: Mixed carboxylic phosphoric anhydrides 3, formed from 3′-nucleotides 1 and amino acid N-carboxyanhydrides 2, undergo competing rearrangement to 2′-aminoacyl esters 4 and cyclization to 2′,3′-cyclic phosphates 5. The intramolecular aminoacyl transfer is faster than the cyclization despite the ease with which 2′,3′-cyclic phosphates are formed through any other form of phosphate activation.
