The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group

Mikkola, Satu; Stenman, Eeva; Nurmi, Kirsi; Yousefi-Salakdeh, Esmail; Strömberg, Roger; Lönnberg, Harri

doi:10.1039/a903691a

Cited by 64 publications

(57 citation statements)

References 42 publications

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“…On the other hand, as a Lewis acid, Zn 2+ ion activates the substrate HPNP by coordinating P-O − anion and increasing the charges density of positive phosphorus atom which serves as a receptor of the nucleophilic C2-oxygen anion of HPNP; (2) another function of Zn 2+ ion is to lower the pK a values of the coordinated water molecule, and provides a higher concentration of the effective intramolecular general base at neutral pH and accelerates the deprotonated process of the C2-hydroxyl of HPNP. As a result, the HPNP hydrolytic cleavage is readily accelerated through a pseudo-intramolecular nucleophilic attack of C2-oxygen anion on phosphorus atoms of phosphate moiety of HPNP; (3) the third possible role of metal ion in the hydrolysis of phosphate esters is related to the stabilization of the reaction transition state [37][38][39]. In our case, the divalent zinc ion can stabilize the negative transition state and then lower the reaction activation energy; thus, HPNP cleavage is accelerated.…”

Section: Proposed Mechanism Of Hpnp Cleavage By the Zn(ii)-biap Complexmentioning

confidence: 82%

“…Nevertheless, in the cleavage reaction of HPNP, the cleavage mechanism does not involve a direct nucleophilic attack by metal-coordinated hydroxide, which participates as a base for the deprotonation of a substrate alcohol group serving as the intramolecular nucleophile [25][26][27][28][29][30].…”

Section: Proposed Mechanism Of Hpnp Cleavage By the Zn(ii)-biap Complexmentioning

confidence: 99%

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Cleavage of phosphate diesters mediated by Zn(II) complex in Gemini surfactant micelles

Jiang

Lin

et al. 2007

Journal of Colloid and Interface Science

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Section: Proposed Mechanism Of Hpnp Cleavage By the Zn(ii)-biap Complexmentioning

confidence: 82%

Section: Proposed Mechanism Of Hpnp Cleavage By the Zn(ii)-biap Complexmentioning

confidence: 99%

Cleavage of phosphate diesters mediated by Zn(II) complex in Gemini surfactant micelles

Jiang

Lin

et al. 2007

Journal of Colloid and Interface Science

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“…Metal aqua ions have been shown to accelerate the cleavage of ribonucleoside 3'-phosphodiesters by serving as an intramolecular general acid catalyst that donates a proton to the departing 5'-oxygen upon the rate-limiting breakdown of the phosphorane intermediate obtained by an attack of the 2'-oxy anion on the P-atom [22]. Several factors may contribute to the higher catalytic activity of the bimetallic species.…”

mentioning

confidence: 98%

Bimetallic Complexes of Spiro‐Azacrown Ligands as Catalysts of Phosphoester and Phosphoric Anhydride Cleavage

Wang

Mikkola²,

Lönnberg³

2004

Chemistry & Biodiversity

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The ability of bimetallic homo- and heteronuclear complexes of two spiro-linked ligands, viz. a biazacrown (i.e., 2,6,10,14,18,22-hexaazaspiro[11.11]tricosane (1)) and an azacrown-crown ether (i.e., 14,17,20,23,26-pentaoxa-2,6,10-triaza-spiro[11.15]heptacosane (2)), to promote the cleavage of the phosphoester linkage of dinucleoside 3',5'-phosphates and the phosphoric anhydride bridge of dinucleoside 5',5'-triphosphates was studied. In both reactions, the bimetallic homonuclear Cu2+ and Zn2+ complexes were better catalysts than their monometallic counterparts. The acceleration was two- to five-fold with the phosphoester cleavage and 3- to 20-fold with the phosphoric anhydride cleavage. Interestingly, the most-efficient catalyst of the phosphoester cleavage was the heterodinuclear Ni2+,Zn2+ complex of 1, the catalytic activity of which was up to 5- and 100-fold that of the homodinuclear Zn2+ and Ni2+ complexes, respectively. Moreover, this cooperative acceleration was observed to depend on the identity of the 5'-linked nucleoside: 3',5'-UpU and 3',5'-ApU were cleaved much faster than 3',5'-UpA, and no cooperative acceleration was observed with 3',5'-ApA. The reaction was second-order in hydroxide ion concentration, suggesting that a double deprotonation took place on going from the initial to the transition state. Evidently, in addition to deprotonation of the attacking 2'-OH group, N(3)H of the 5'-linked uridine was displaced by one of the metal ions of the cleaving agent. With the phosphoric anhydride cleavage, no similar cooperativity of two different metal ions was observed, but the greatest rate-acceleration was achieved with the homodinuclear Cu2+ complexes.

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“…It is known 21,31,33 that RNA hydrolysis shows an enhancement due to the presence of divalent cations, and that this enhancement is a function of the ionic environment including pH. For pneumococcal poly- saccharides 6A and 6B, Zon et al 13 also observed an enhancement in the presence of Ca 2ϩ .…”

Section: Effect Of Mgclmentioning

confidence: 91%

Base hydrolysis of phosphodiester bonds in pneumococcal polysaccharides

et al. 2004

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A comprehensive study of the base hydrolysis of all phosphodiester bond-containing capsular polysaccharides of the 23-valent pneumococcal vaccine is described here. Capsular polysaccharides from serotypes 6B, 10A, 17F, 19A, 19F, and 20 contain a phosphodiester bond that connects the repeating units in these polysaccharides (also referred to as backbone phosphodiester bonds), and polysaccharides from serotypes 11A, 15B, 18C, and 23F contain a phosphodiester bond that links a side chain to their repeating units. Molecular weight measurements of the polysaccharides, using high performance size exclusion chromatography with tandem multiangle laser light scattering and refractive index detection, was used to evaluate the kinetics of hydrolysis. The measurement of molecular weight provides a high degree of sensitivity in the case of small extents of reaction, thus allowing reliable measurements of the kinetics over short times. Pseudo-first-order rate constants for these polysaccharides were estimated using a simple model that accounts for the polydispersity of the starting sample. It was found that the relative order of backbone phosphodiester bond instability due to base hydrolysis was 19A > 10A > 19F > 6B > 17F, 20. Degradation of side-chain phosphodiester bonds was not observed, although the high degree of sensitivity in measurements is lost in this case, due to the low contribution of the side chains to the total polysaccharide molecular weight. In comparison with literature data on pneumococcal polysaccharide 6A, 19A was found to be the more labile, and hence appears to be the most labile pneumococcal polysaccharide studied to date. The rate of hydrolysis increased at higher pH and in the presence of divalent cation, but the extent was lower than expected based on similar data on RNA. Finally, the differences in the phosphodiester bond stabilities were analyzed by considering stereochemical factors in these polysaccharides. These results also provide a framework for evaluation of molecular integrity of phosphodiester-bond-containing polysaccharides in different solution conditions.

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The mechanism of the metal ion promoted cleavage of RNA phosphodiester bonds involves a general acid catalysis by the metal aquo ion on the departure of the leaving group

Cited by 64 publications

References 42 publications

Cleavage of phosphate diesters mediated by Zn(II) complex in Gemini surfactant micelles

Cleavage of phosphate diesters mediated by Zn(II) complex in Gemini surfactant micelles

Bimetallic Complexes of Spiro‐Azacrown Ligands as Catalysts of Phosphoester and Phosphoric Anhydride Cleavage

Base hydrolysis of phosphodiester bonds in pneumococcal polysaccharides

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