35931-57-8Relevant academic research and scientific papers
The synthesis of di- and oligo-nucleotides containing a phosphorodithioate internucleotide linkage with one of the sulfur atoms in a 5′-bridging position
Olesiak, Magdalena,Stec, Wojciech J.,Okruszek, Andrzej
experimental part, p. 2162 - 2169 (2009/09/04)
A new type of internucleotide phosphorodithioate linkage is described, wherein one of the sulfur atoms occupies a 5′-bridging position. Representative dinucleotides possessing such a bond were synthesized by S-alkylation of nucleoside-3′-O-phosphorodithio
Synthesis and properties of diuridine phosphate analogues containing thio and amino modifications
Thomson, James B.,Patel, Bhisma K.,Jimenez, Victor,Eckart, Klaus,Eckstein, Fritz
, p. 6273 - 6281 (2007/10/03)
Several analogues of diuridine phosphate (UpU) were synthesized in order to investigate why replacing the 2'-hydroxyl with a 2'-amino group prevents hydrolysis. These analogues were designed to investigate what influence the 2'-substituent and 5'-leaving group have upon the rate of hydrolysis. All the analogues were considerably more labile than UpU toward acid-base-catalyzed hydrolysis. In the pH region from 6 to 9, the rate of hydrolysis of uridylyl (3'-5') 5'-thio-5'deoxyuridine (UpsU) hydrolysis rose, in a log linear fashion, from a value of 5 x 10-6 s-1 at pH 6 to 3200 x 10-6 s-1 at pH 9, indicating that attack on the phosphorus by the 2'-oxo anion is rate-limiting in the hydrolysis mechanism. In contrast, the rate of uridylyl (3'-5') 5'-amino-5'deoxyuridine (UpnU) hydrolysis fell from a value of 1802 x 10-6 s-1 at pH 5 to 140 x 10-6 s-1 at pH 7.5, where it remained constant up to pH 11.5, thus indicating an acid-catalyzed reaction. The analogue 2'-amino-2'-deoxyuridylyl (3'-5') 5'-thio-5'-deoxyuridine (amUpsU) was readily hydrolyzed above pH 7, in contrast to the hydrolytic stability of amUpT, with rates between 85 x 10-6 s-1 and 138 x 10-6 s-1. The hydrolysis of 2'-amino-2'-deoxyuridylyl (3'-5') 5'-amino-5'-deoxythymidine (amUpnT) rose from 17 x 10-6 s-1 at pH 11.5 to 11 685 x 10-6 s-1 at pH 7.0, indicating an acid-catalyzed reaction, where protonation of the 5'-amine is rate limiting. The cleavage rates of UpsU, UpnU, and amUpsU were accelerated in the presence of Mg2+,Zn2+, and Cd2+ ions, but a correlation with interaction between metal ion and leaving group could only be demonstrated for amUpsU. UpsU and UpnU are also substrates for RNase A with UpsU having similar Michaelis-Menten parameters to UpU. In contrast, UpnU is more rapidly degraded with an approximate 35-fold increase in catalytic efficiency, which is reflected purely in an increase in the value of κ(cat).
