633-90-9Relevant academic research and scientific papers
Prebiotically Plausible RNA Activation Compatible with Ribozyme-Catalyzed Ligation
Song, Emilie Yeonwha,Jiménez, Eddy Ivanhoe,Lin, Huacan,Le Vay, Kristian,Krishnamurthy, Ramanarayanan,Mutschler, Hannes
, p. 2952 - 2957 (2021)
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.
Direct phosphorylation of nucleosides by oxyphosphorane
Chen, Xin,Zhang, Nan-Jing,Li, Yan-Mei,Jiang, Yang,Zhang, Xiang,Zhao, Yu-Fen
, p. 1615 - 1618 (1997)
Ester exchange reaction of oxyphosphorane 1 with unprotected ribonucleosides cytidine 2a and adenosine 2b generated selectively spirooxyphosphoranes 3a and 3b respectively. Upon hydrolysis, the labile spirooxyphosphoranes were converted into stable ribonucleoside 2',3'-cyclic monophosphates 4a and 4b in good yields. Some polyribonucleotides were also detected from the hydrolytic products. Reaction of 1 with a 2'-deoxyribonucleoside such as thymidine 5 followed by hydrolysis afforded thymidine acyclic monophosphates (7, 8). Hence, the ester exchange reaction of oxyphosphorane might provide an efficient one-pot phosphorylation methodology for ribonucleosides and 2'-deoxyribonucleosides without any protection.
Guanidine based self-assembled monolayers on Au nanoparticles as artificial phosphodiesterases
Salvio, Riccardo,Cincotti, Antonio
, p. 28678 - 28682 (2014/07/22)
Gold nanoparticles passivated with a long chain alkanethiol decorated with a phenoxyguanidine moiety were prepared and investigated as catalysts in the cleavage of the RNA model compound HPNP and diribonucleoside monophosphates. The catalytic efficiency and the high effective molarity value of the Au monolayer protected colloids points to a high level of cooperation between the catalytic groups.
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.
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.
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.
Kinetic analysis of the cleavage of the ribose phosphodiester bond within guanine and cytosine-rich oligonucleotides and dinucleotides at 65-200 °C and its implications concerning the chemical evolution of RNA
Kawamura, Kunio
, p. 153 - 162 (2007/10/03)
A monitoring method of rapid hydrothermal reactions was successfully applied to a kinetic analysis of the cleavage of a ribose phosphodiester bond within oligonucleotides and dinucleotides at 150-200 °C. The apparent rate constants (kapp) of degradation of the ribose 3′,5′-cytidylylguanosine sequence (-C3′pGd-) within oligonucleotides and dinucleotides were determined, where the -C3′pGd- sequence in oligonucleotides is less stable than 2′,5′-cytidylylguanosine (C2′pG) and 3′,5′-cytidylylguanosine (C3′pG). It was unexpected that the stability of the target sequence would be dependent on the surrounding sequences of the oligonucleotides, although the temperatures used in the study were extremely higher than the melting points. The stability of a phosphodiester bond of 2′-deoxycytidylyl-2′-deoxyguanosine (CdpGd) is much higher than that of a ribose phosphodiester bond at low temperatures, but becomes comparable at 200 °C. During the degradation of C2′pG or C3′pG, interconversion between C2′pG and C3′pG was observed along with cleavage of the phosphodiester bond. Based on an analysis of the extent of interconversion, the apparent rate constants of the disappearance of C2′pG and C3′pG were dissected into the rate constants of hydrolysis (khy) and interconversion (kint), where the values of khy were greater than those of kint. The apparent activation energy of the degradation of the target sequence was 100-109 kJ mol-1 for oligonucleotides, 90 kJ mol-1 for C3′pG, and 87 kJ mol-1 for C2′pG, and 139 kJ mol-1 for CdpGd. The apparent activation enthalpy and entropy changes of the degradation of the target sequence were also determined; the values of the activation parameter were ΔHapp = 94-105 kJ mol-1 and ΔSapp= -(36-59) J mol-1 T-1 for five oligonucleotides, ΔHapp = 86 kJ mol-1 and ΔSapp = -97 J mol-1 T-1 for C3′pG, ΔHapp = 84 kJ mol-1, ΔXSapp = - 105 J mol-1 T-1 for C2′pG, and ΔHapp = 135 kJ mol-1, ΔSapp = +2 J mol-1 T-1 for CdpGd. The activation parameters, ΔHapp and ΔSapp, for the oligonucleotides increased with the length of the surrounding sequence of -C3′pGd-; this fact clearly demonstrates the existence of the influence of the surrounding sequence for the stability of the target ribose phosphodiester bond. Based on a kinetic analysis, the reaction mechanism of the degradation of the ribose phosphodiester bond at high temperatures is discussed. Furthermore, possible pathways of the chemical evolution of RNA are discussed from the viewpoint of the hydrothermal origin of life.
Zn2+ -promoted hydrolysis of 3',5'-dinucleoside monophosphates and polyribonucleotides. The effect of nearest neighbours on the cleavage of phosphodiester bonds
Kuusela, Satu,Loennberg, Harri
, p. 1669 - 1678 (2007/10/03)
Pseudo first-order rate constants for the Zn2+ -promoted cleavage of 15 different dinucleoside monophosphates, 4 different ribo homopolymers and RNA III from baker's yeast have been determined. Furthermore, the distribution of various nucleosides at the 3'- and 5'-terminus of the oligomeric hydrolysis products of RNA has been quantified. On these bases, the effect of nearest neighbours on the metal-ion-promoted hydrolysis of the internucleosidic phosphodiester bonds of RNA is discussed.
