2415-43-2Relevant articles and documents
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Smrt,Holy
, p. 981 (1967)
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Chemistry and structure of modified uridine dinucleosides are determined by thiolation
Smith, Wanda S.,Sierzputowska-Gracz, Hanna,Sochacka, Elzbieta,Malkiewicz, Andrzej,Agris, Paul F.
, p. 7989 - 7997 (1992)
The structural determination of modified nucleosides is important for understanding the chemistry, structure, and functional changes that they introduce to the nucleic acids in which they occur. Thiolation of transfer RNA wobble position uridine produces an energetically stabilized conformation of the nucleoside in solution at ambient temperature that is independent of the nature of the 5-position substituent and is of biological significance to tRNA selection of only those codons ending in adenosine (Sierzputowska-Gracz, H.; Sochacka, E.; Malkiewicz, A.; Kuo, K.; Gehrke, C.; Agris, P. F. J. Am. Chem. Soc. 1987, 109, 7171-7177. Agris, P. F.; Sierzputowska-Gracz, H.; Smith, W.; Malkiewicz, A.; Sochacka, E.; Nawrot, B. J. Am. Chem. Soc., in press). Dinucleoside monophosphates have been synthesized as models for investigating the conformations and structures of wobble position uridine-34 that is thiolated and differently modified at position-5 and that is either 3′-adjacent to the invariant uridine-33 in tRNA or 5′-adjacent to the second anticodon position uridine-35. The structures and conformations of 11 dinucleoside monophosphates were analyzed by 1H, 13C, and 31P magnetic resonance (NMR) spectroscopy. Within the dinucleosides, the individual modified uridine structures and conformations were very similar to those of their respective mononucleosides. The 2-position thiolation, and not the 5-position modification, produced a significantly more stable, C(3′) endo, gauche+, anti conformer. However, within those dinucleosides in which the 2-thiouridine was 5′ to the unmodified uridine, the nucleic acid backbone torsion angles of the unmodified uridine 5′-phosphate were affected, as determined from the scalar coupling constants J1H1H, J1H31P, and J13C31P. In contrast, uridines that were only 5-position modified did not affect the conformation of the 3′-adjacent unmodified uridine phosphate. The structural data obtained and the nucleoside conformations derived from the data support the "modified wobble hypothesis" (Agris, P. F. Biochimie 1992, 73, 1345-1349); i.e., the tRNA wobble position-34 nucleoside is modified in such a way as to constrain not only its own conformation but also the structural conformation of the anticodon, thereby producing a specific codon selection during protein synthesis.
The protection of hydroxyl groups in diribonucleoside phosphates.
Smrt
, p. 3133 - 3134 (1967)
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Oligoribonucleotide synthesis by the use of 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group
Umemoto, Tadashi,Wada, Takeshi
, p. 9529 - 9531 (2007/10/03)
A novel method for the synthesis of oligoribonucleotide using 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group has been developed. A novel method for the synthesis of oligoribonucleotides using 1-(2-cyanoethoxy)ethyl (CEE) as a 2′-hydroxy protecting group has been developed. A CEE group was introduced to the 2′-position of N-acyl-3′,5′-O-silyl-protected ribonucleosides under acidic conditions in good yields. The 2′-O-CEE group was found to be stable in an aqueous or ethanolic ammonia and was quickly removed by treatment with anhydrous tetrabutylammonium fluoride (TBAF). A combination of the use of N-acyl and 2′-O-CEE protecting groups enabled a reliable and complete two-step deprotection, first with NH3-EtOH, then with TBAF in THF, without cleavage of internucleotidic linkages.
Metal-Ion-Promoted Cleavage, Isomerization, and Desulfurization of the Diastereomeric Phosphoromonothioate Analogues of Uridylyl(3′,5′)uridine
Ora, Mikko,Peltomaeki, Markku,Oivanen, Mikko,Loennberg, Harri
, p. 2939 - 2947 (2007/10/03)
Metal-ion-promoted hydrolytic reactions of the SP and RP diastereomers of the phosphoromonothioate analogues of uridylyl(3′,5′)uridine [3′,5′-Up(s)U] and their cleavage products, diastereomeric uridine 2′,3′-cyclic phosphates [2′,3′-cUMPS], were followed by HPLC as a function of pH (4.7-5.6) and metal ion concentration (1-10 mmol L-1). With 3′,5′-Up(s)U, three reactions compete: (i) cleavage to 2′,3′-cUMPS, (ii) isomerization to 2′,5′-Up(s)U, and (iii) desulfurization to an equilibrium mixture of 2′,5′- and 3′,5′-UpU. Of these, the cleavage to 2′,3′-cUMPS is markedly accelerated by Zn2+, Cd2+, and Gd3+, the rate enhancements observed with the Sp isomer at [Mz+] = 5 mmol L-1 and pH 5.6 (T = 363.2 K) being 410-, 3600-, and 2000-fold, respectively. The effect of Mn2+ and Mg2+ on the cleavage rate is, in turn, modest (6- and 1.7-fold acceleration, respectively). The rate-accelerations are almost equal with the SP and RP diastereomers. The metal-ion-promoted reaction is first-order in both the hydroxide and metal ion concentration, and it proceeds by inversion of configuration at phosphorus, consistent with an in-line displacement mechanism. The isomerization and desulfurization are much less susceptible to metal ion catalysis: 6.4- and 7.7-fold accelerations were observed with Zn2+, respectively. Gd3+ does not promote these reactions at all. The isomerization proceeds by retention of configuration at phosphorus, consistent with formation of a pentacoordinated thiophosphorane intermediate having the entering 2′-hydroxy group apical and the leaving 3′-hydroxy equatorial, and subsequent pseudorotation posing the leaving group apical. The hydrolysis of 2′,3′-cUMPS is accelerated by metal ions slightly more efficiently than the cleavage of 3′,5′-Up(s)U to 2′,3′-cUMPS. In striking contrast to the reactions of 3′,5′-Up(s)U, the hydrolytic desulfurization to 2′,3′-cUMP is accelerated as efficiently as its endocyclic hydrolysis to uridine 2′and 3′-phosphoromonothioates [2′- and 3′-UMPS]. Somewhat unexpectedly, the latter compounds were observed to undergo metal-ion-promoted cyclization/desulfurization to 2′,3′-cUMP. The hydrolysis of 2′- or 3′-UMPS to uridine was, in turn, observed to be retarded by metal ions. The mechanisms of the partial reactions are discussed.
