13493-13-5Relevant articles and documents
Hydrolytic reactions of the phosphorodithioate analogue of uridylyl(3',5')uridine: Kinetics and mechanisms for the cleavage, desulfurization, and isomerization of the internucleosidic linkage
Ora, Mikko,Jaervi, Johanna,Oivanen, Mikko,Loennberg, Harri
, p. 2651 - 2657 (2000)
The hydrolytic reactions of the phosphorodithioate analogue of uridylyl(3',5')uridine [3',5'-Up(s)2U] were followed by HPLC over a wide pH range at 363.2 K. Under acidic and neutral conditions, three reactions compete: (i) desulfurization to a mixture of the (R(P))- and (S(P))- diastereomers of the corresponding 3',5'- and 2',5'-phosphoromonothioates [3',5'- and 2',5'-Up(s)U], which are subsequently desulfurized to a mixture of uridylyl(3',5')- and -(2',5')uridine [3',5'- and 2',5'-UpU], (ii) isomerization to 2',5'-Up(s)2U, and (iii) cleavage to uridine, in all likelihood via a 2',3'-cyclic phosphorodithioate (2',3'-cUMPS2). Under alkaline conditions (pH > 8), only a hydroxide ion catalyzed hydrolysis to uridine via 2',3'-cUMPS2 takes place. At pH 3-7, all three reactions are pH- independent, the desulfurization being approximately 1 order of magnitude faster than the cleavage and isomerization. At pH 2U is comparable to that of (S(P))- and (R(P))- 3',5'-Up(s)U (and to that of 3',5'-UpU, except at pH 2U is 37% and 53% of that of (S(P))- and (R(P))-3',5'-Up(s)U, respectively. The reactions, however, differ with the respect of the product accumulation. While the phosphoromonothioates produce a mixture of 2'- and 3'-thiophosphates as stable products, 3',5'-Up(s)2U is hydrolyzed to uridine without accumulation of the corresponding dithiophosphates. At pH 2U, but the reactivity difference decreases on going to less acidic solutions. In summary, the hydrolytic stability of 3',5'-Up(s)2U closely resembles that of the corresponding phosphoromonothioate. While replacing one of the nonbridging phosphate oxygens of 3',5'-UpU with sulfur stabilizes the phosphodiester bond under acidic conditions by more than 1 order of magnitude, the replacement of the remaining nonbridging oxygen has only a minor influence on the overall hydrolytic stability.
On the Mechanism of Buffer-Catalyzed Hydrolysis of RNA Models
Perrin, Charles L.
, p. 1239 - 1243 (1995)
An alternative mechanism is proposed for the simultaneous hydrolysis and isomerization of 3',5''-uridyluridine and related dialkyl phosphates in agueous morpholine buffers, which was studied by Breslow and Xu.This alternative mechanism leads to kinetic equations that reproduce the experimental data.
Buffer catalyzed cleavage of uridylyl-3′,5′-uridine in aqueous DMSO: Comparison to its activated analog, 2-hydroxypropyl 4-nitrophenyl phosphate
Lain,L?nnberg,L?nnberg
, p. 3484 - 3492 (2015/03/18)
Buffer catalysis of the cleavage and isomerization of uridylyl-3′,5′-uridine (UpU) has been studied over a wide pH range in 80% aq. DMSO. The diminished hydroxide ion concentration in this solvent system made catalysis by amine buffers (morpholine, 4-hydroxypiperidine and piperidine) visible even at relatively low buffer concentrations (10-200 mmol L-1). The observed catalysis was, however, much weaker than what has been previously reported for the activated RNA model 2-hydroxypropyl 4-nitrophenyl phosphate (HPNP) in the same solvent system. In the case of morpholine, contribution of both the acidic and the basic buffer constituent was significant, whereas with 4-hydroxypiperidine and piperidine participation of the acidic constituent could not be established unambiguously. The results underline the importance of using realistic model compounds, along with activated ones, in the study of the general acid/base catalysis of RNA cleavage.
Preparation and cleavage reactions of 3′-thiouridylyl-(3′→5′)-uridine
Liu, Xiaohai,Reese, Colin B.
, p. 2227 - 2236 (2007/10/03)
3′-Thiouridylyl-(3′→5′)-uridine [(Us)pU] 3 is prepared by coupling together the disulfide 14 and the 5′-H-phosphonate 18, and then removing the protecting groups. (Us)pU 3 readily undergoes cleavage in 0.05 mol dm-3 sodium glycinate buffer (pH 10.06) at 50 °C to give, in the first instance, uridine 4 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21; in glacial acetic acid at 30 °C, it rapidly undergoes cleavage in essentially the same way. The behaviour of (Us)pU 3 is compared with that of uridylyl-(3′→5′)-uridine (UPU) 1a under the same basic and acidic reaction conditions. (Us)pU 3 and 3′-thiouridine 2′,3′-cyclic phosphorothioate 21 are both substrates for ribonuclease A; (Us)pU 3 is a substrate for Crotalus adamanteus snake venom phosphodiesterase but not for calf spleen phosphodiesterase.
