The SYNTHESIS OF Α,γ-Dinucleoside TRIPHOSPHATES. THE CONFRONTED NUCLEOTIDE STRUCTURE FOUND AT THE 5′-Terminus OF EUKARYOTE MESSENGER RIBONUCLEIC ACID

Abstract

α,γ-Dinucleoside triphosphates showing the recently discovered modified structure at the 5′-terminus of eukaryote mRNA were synthesized by use of a new method employing di-n-butylphosphinothioyl bromide.

Molecular design of a eukaryotic messenger RNA and its chemical synthesis

“…Eukaryotic mRNAs have a cap structure (m7G5'pppNNN...) at their 5'-terminus. This structure was first found by Miura (1) in 1975 from cytoplasmic polyhedrosis virus and the structure was confirmed by its chemical synthesis (2)(3)(4)(5). This cap structure is known to act in the important role of binding mRNAs to ribosome (6-8) and for the stabilization of mRNAs against 5'-exonucleases (9,10).…”

“…ammonia as shown in Scheme I. For the construction of the cap structure at its 5'-terminus, it was converted into the phosphorimidazolide (3) and reacted with the capping agent (ppm7GTMTrmM) (4). Finally, whole protecting groups were removed under acidic conditions to afford the capped 9-mer, m7G5'pppGUAUUAAUA (5, F-1).…”

Chemical synthesis of the 5′-terminal part bearing cap structure of messenger RNA of cytoplasmic polyhedrosis virus (CPV): m7G5′ pppAmpG and m7G5pppAmpGpU

“…The organic extracts were combined, dried over sodium sulfate, and concentrated in vacuo. The residue was chromatographed on silica gel column (ethyl acetate) to afford MMTrAZ (1.10 g, 60%): NMR(CDC13),'3.52(3H, s, 2'-O-CH3), 3.77(3H, 9.96%. To a mixture of MWTrAlz (146 mg, 0.22 mmol) and cyclohexylammonium S,S-di-4-methoxyphenyl phosphorodithioate (1.19 g, 0.27 mmol) in dry pyridine (1 ml) was added TPS (160 mg, 0.53 mmol) and the solution was stirred at room temperature for 3 days.…”

Design and Synthesis of New Cap Analogs Containing 2-OH Modifications on Both Guanosine and m7Guanosine Moieties

“…It is to be noted that mRNAs possessing correctly incorporated caps, i.e., m 7 G [5 ] [11]. Although the synthetic conventional cap analog, m 7 G[5 ]ppp [5 ]N has been known for the last three decades [12], the first syntheses of cap analogs with 3 -OH modification on m 7 G moiety such as m 2 [5 ]G and m 7 3 dG [5 ]ppp [5 ]G were reported by Stepinski et al in 2001 [13]. It is noteworthy that these analogs are incorporated exclusively in the forward orientation and the reverse orientation is not possible because of the absence of free 3 -OH group on m 7 G moeity and these analogs are called "antireverse" cap analogs (ARCA) [13,14].…”