Pyrimidine ribonucleoside phosphorylase activity vs 5- and/or 6-substituted uracil and uridine analogues, including conformational aspects

Defining a process operating window for the synthesis of 5-methyluridine by transglycosylation of guanosine and thymine

“…One of the potential problems with transglycosylation is that both reactions are reversible and a strategy is required to drive the reactions in the desired direction. An advantage of using guanosine as the donor nucleoside is that the resulting guanine precipitates from the reaction as a result of low water solubility (<0.01%, m/m at 80 • C) and therefore shifts the equilibrium away from the reverse reaction (Scheme 1b), although it appears that the equilibrium of the UP catalysed reaction may provide a more significant contribution (Visser et al, 2010b;Leer et al, 1977;Krajewska and Shugar, 1982).…”

Crystallization and preliminary X-ray study ofVibrio choleraeuridine phosphorylase in complex with 6-methyluracil

“…A. The ability of uridine phosphorylase to implement the catalytic reaction using pyrimidine substrates with alkyl or halogen substituents at the 5-position has been demonstrated, and these reactions are reversible (Krajewska & Shugar, 1982;Leer et al, 1977;Temmink et al, 2007;Watanabe & Uchida, 1995;Woodman et al, 1980). However, in the case of 6-alkyl-substituted pyrimidines (for example, 6-methyluracil) the reaction only proceeds in the direction of phosphorolysis of a nucleoside analogue (P; Fig.…”

“…However, in the case of 6-alkyl-substituted pyrimidines (for example, 6-methyluracil) the reaction only proceeds in the direction of phosphorolysis of a nucleoside analogue (P; Fig. 1b), and the synthesis of nucleoside analogues (S) does not occur (Krajewska & Shugar, 1982). Krajewska and Shugar assumed that the hydrophobic chemical group attached to the aromatic ring at the 6-position of pyrimidine does not allow the hydrophilic phosphate group of ribose 1-phosphate to move closer to the N1 atom of the heterocycle.…”

1-(β-D-Ribofuranosyl)-6-propylcytosine

“…6-thiocarboxamide-UMP, a structural analogue of orotidine-5'-phosphate (OMP), is a potent inhibitor of OMP decarboxylase (Cody & Kalman, 1985), and (b) model compounds to determine whether the parent non-substituted nucleoside (or nucleotide) is involved in a given enzymatic reaction in the syn and/or anti conformation, e.g. several 6-substituted uridines are reasonable substrates for uridine phosphorylase (Krajewska & Shugar, 1982;Felczak et al, 1996), pointing to involvement of the syn conformation of uridine as an intermediate in the reaction. This led to determination of the structures of a variety of 6-substituted uracil nucleoside analogues (Felczak et al, 1996, and references cited), and the solid-state structure of one cytosine nucleoside analogue, 1-(,~-D-arabinofuranosyl)-6-methylcytosine (Yamaguchi et al, 1992).…”