Synthesis of novel mRNA 5′ cap-analogues: Dinucleoside P 1, P3-tri-, P1, P4-tetra-, and P1, P5-pentaphosphates

Abstract

A series of new mRNA anti reverse cap analogues (ARCA) was designed to obtain a tool for studying the mechanism of protein translation. Dinucleoside P1, P3-tri-, P1, P4-tetra- and P1, P5-pentaphosphates, linked by a 5′-to-5′ phosphate bridge and composed of modified 7-methylguanosine and guanosine, have been synthesized. The hydroxyl group (2′OH or 3′OH) in 7-metylguanosine moiety was replaced by -OCH3 or -H in order to obtain the cap analogues capable to be correctly incorporated into synthetic mRNA transcripts. Tri-, tetra-, and pentaphosphates were prepared by ZnCl 2 catalyzed condensation in DMF of derivatives of the 7-methylguanosine diphosphates with the guanosine mono-, di- and triphosphate P-imidazolides, respectively. The structures of the novel compounds were established by means of 1H and 31P NMR spectra.