ChemInform Abstract: New Syntheses of 2′‐C‐Methylnucleosides Starting from D‐Glucose and D‐Ribose.

Beigelman, Leon N.; Ermolinsky, Boris S.; Gurskaya, G. V.; Tsapkina, E. N.; Karpeisky, M.Ya.; Mikhailov, S. N.

doi:10.1002/chin.198810382

Cited by 2 publications

(2 citation statements)

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“…Synthesis of 2'-MeADP and 2'-MeUDP. 2'-C-Methyladenosine and 2'-C-methyluridine were prepared by following the procedure of Beigelman et al (1987Beigelman et al ( , 1988. The nucleosides were purified using Dowex 1-X2 (hydroxide form) as described by Dekker (1965).…”

Section: Methodsmentioning

confidence: 99%

2'-C-Methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii

Ong¹,

McFarlan²,

Hogenkamp³

1993

Biochemistry

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The interaction of the adenyosylcobalamin-dependent ribonucleoside diphosphate reductase of Cornyebacterium nephridii with 2'-C-methyladenosine 5'-diphosphate (2'-MeADP) and 2'-C-methyluridine 5'-diphosphate (2'-MeUDP) has been investigated. The nucleotide analogs are converted to adenine and uracil, respectively, suggesting that they may be mechanism-based inhibitors. In addition, both analogs generate nucleotides with properties expected for the 2'-deoxy-2'-C-methylnucleotides. The nucleoside obtained after enzymatic dephosphorylation of the product formed from 2'-MeADP has been identified as 2'-deoxy-2'-C-methyladenosine by 1H NMR and mass spectroscopies. Adenine is the major product derived from 2'-MeADP, indicating that the degradation pathway predominates. During the reaction, the carbon-cobalt bond of the coenzyme is cleaved irreversibly to yield 5'-deoxyadenosine and cob(II)alamin. 2'-MeADP is a potent competitive inhibitor of the reduction of the purine nucleotides ADP and GDP, while 2'-MeUDP competitively inhibits the reduction of the pyrimidine nucleotides UDP and CDP. 2'-MeADP is a very effective promoter of the tritium exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the exchange reaction is an integral part of the overall reduction. All these observations are consistent with the reaction mechanism proposed by Stubbe and co-workers [Harris, G., Ashley, G. W., Robins, M. J., Tolman, R. L., & Stubbe, J. (1987) Biochemistry 26, 1895-1902 (1987); Stubbe, J. (1990) J. Biol. Chem. 265, 5329-5332] in which they suggest that the partitioning between reduction and inactivation occurs at the level of the 2'-deoxy-3'-ketoribonucleotide intermediate.

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Section: Methodsmentioning

confidence: 99%

2'-C-Methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii

Ong¹,

McFarlan²,

Hogenkamp³

1993

Biochemistry

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“…The syrupy triacetate 6 (1.55 g, 3.9 mmol) was condensed with M-benzoyladenine in the presence of hexamethyldisilazane and (trimethylsilyl)trifluoromethanesulfonate as described by Beigelman et al (1988) to yield 9-(2,3-di-0-acetyl-5-0-benzoyl-3-C-methyl-^-D-ribofuranosyl)-iV6-benzoyladenine (7) in 54% yield (1.2 g, 2.1 mmol). Condensation of 6 (1.55 g, 3.9 mmol) with uracil using the same procedure gave 950 mg (2.1 mmol, 53%) of l-(2,3-di-0-acetyl-5-0benzoyl-3-C-methyl-/S-D-ribofuransoyl)uracil (11).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii

Ong¹,

Nelson²,

Hogenkamp³

1992

Biochemistry

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Two nucleoside diphosphate analogs, 3'-C-methyl-ADP and 3'-C-methyl-UDP, have been tested as substrate and/or allosteric effectors using the adenosylcobalamin-dependent ribonucleoside diphosphate reductase of Corynebacterium nephridii. Neither analog was a substrate for the reductase. However, they did function as allosteric effectors and as inhibitors of the reduction of ADP and UDP, respectively. The nucleotide analogs did not stimulate the hydrogen exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the cleavage of the 3'-carbon-hydrogen bond is a prerequisite for the exchange reaction. A reinvestigation of the requirements for the exchange reaction revealed that the deoxyribonucleoside diphosphate products are very effective promoters of this reaction. Indeed, the deoxyribonucleoside diphosphates were found to be more effective in promoting the exchange reaction than the ribonucleoside diphosphate substrates. In contrast, the deoxyribonucleoside triphosphate effectors, dATP, dUTP, and dTTP, were only marginally effective as promoters of this reaction.

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ChemInform Abstract: New Syntheses of 2′‐C‐Methylnucleosides Starting from D‐Glucose and D‐Ribose.

Abstract: The 2‐C‐methyl‐D‐ribofuranose derivative (IIb) is prepared via two reaction pathways from the branched‐chain sugars (I) or (VIa) which are obtained from D‐glucose or D‐ribose by known methods.

Cited by 2 publications

References 1 publication

2'-C-Methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii

2'-C-Methyladenosine and 2'-C-methyluridine 5'-diphosphates are mechanism-based inhibitors of ribonucleoside diphosphate reductase from Corynebacterium nephridii

Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii

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