23583-44-0Relevant academic research and scientific papers
Transition state in DNA polymerase β Catalysis: Rate-Limiting chemistry altered by base-pair configuration
Oertell, Keriann,Chamberlain, Brian T.,Wu, Yue,Ferri, Elena,Kashemirov, Boris A.,Beard, William A.,Wilson, Samuel H.,McKenna, Charles E.,Goodman, Myron F.
, p. 1842 - 1848 (2014/04/17)
Kinetics studies of dNTP analogues having pyrophosphate-mimicking β,β-pCXYp leaving groups with variable X and Y substitution reveal striking differences in the chemical transition-state energy for DNA polymerase β that depend on all aspects of base-pairing configurations, including whether the incoming dNTP is a purine or pyrimidine and if base-pairings are right (T*A and G*C) or wrong (T*G and G*T). Br?nsted plots of the catalytic rate constant (log(kpol)) versus pKa4 for the leaving group exhibit linear free energy relationships (LFERs) with negative slopes ranging from -0.6 to -2.0, consistent with chemical rate-determining transition-states in which the active-site adjusts to charge-stabilization demand during chemistry depending on base-pair configuration. The Br?nsted slopes as well as the intercepts differ dramatically and provide the first direct evidence that dNTP base recognition by the enzyme-primer-template complex triggers a conformational change in the catalytic region of the active-site that significantly modifies the rate-determining chemical step.
The Interaction of Trihalogenoacetic Anhydrides and Trihalogenoacetyl Chlorides with Thymidine 5′-Phosphate as an Approach to New Activating Agents in the Phosphorylation Reactions for Nucleotides
Bogachev,Ulanov
, p. 56 - 65 (2007/10/03)
The interaction of thymidine 5′-phosphate with trichloroacetic anhydride, trichloroacetyl chloride, and tribromoacetyl bromide was studied in dimethylformamide and acetonitrile in the presence of tertiary amines. The first two reactions gave the mixed anhydride of trichloroacetic and thymidylic acids (acyl phosphate) as the major product and P1,P 2-dithymidine 5′-pyrophosphate as the byproduct. The third reaction proceeded by a more complicated mechanism and mainly led to substituted polyphosphates. The subsequent treatment of the reaction mixtures with morpholine resulted in thymidine 5′-phosphoromorpholidate in a high yield. The phosphorylating activities of the trichloroacetyl and tribromoacetyl phosphates were 77 and 89%, respectively.
Reaction of Trifluoroacetic Anhydride with Thymidine 5'-Phosphate
Bogachev, V. S
, p. 182 - 186 (2007/10/02)
The interaction of thymidine 5'-phosphate with trifluoroacetic anhydride in an aprotic solvent in the presence of a base is shown to give a mixed anhydride of thymidine 5'-phosphoric and trifluoroacetic acids.The anhydride reacts readily with high yield with various nucleophilic agents (morpholine, p-chlorophenol, pyrophosphate) to form nucleotide derivatives after pretreatment with nucleophilic catalysts (N-methylimidazole, 4-dimethylaminopyridine).Without these catalysts, nucleotide derivatives are not synthesized.A scheme of the reactions is proposed.Key words: trifluoroacetic anhydride, thymidine 5'-phosphate.
