The synthesis of poly-4-thlourldyllc acid and Its effect on protein synthesis In a cell free system derived from rat liver A.A.Hochberg and M.Keren-Zur

The synthesis of poly-4-thiouridylic acid by thiolation of polycytUrytlc acid Is described. A quantitative thiolation was achieved without any cleavage of the phosphodiester bond. The inhibitory effect of the poly-4-thiouridylic acid on protein synthesis in a cell free system derived from rat liver was investigated. INTRODUCTION The use of oligoand polynucleotides as synthetic mRNA has become a useful tool in the investigation of protein synthesis in vitro. Modified polynucleotides however can be used in order to study some specific aspects involved in the complex mechanism of protein synthesis. Several attempts to introduce 4-thiouracil, a sulfur analog of uracil, into oligo-and polynucleotides were reported. Simuth et al. 2 synthesized enzymatically polynucleotides containing 4-thiouridine, by the polymerization of 4-thiouridine-5'-diphosphate with polynucleotide phosphorylase. The 4-thiouridine-5'-diphosphate is a poor substrate for polynucleotide phosphorylase and therefore, the yield of the polymerization product is low. In order to obtain a copolymer of cytldyllcand 4-thiouridylic acid, Favre et al. 3 thlolated polycytldyllc acid with H2S. 36% thiolation was achieved when mild conditions of amino-thiol exchange reaction reported by Miura et al. 4 was used. Recently, Vormbrock et al.