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

Abstract

Synthesis of new cap analogs containing 2 -OH modifications on both guanosine and m 7 guanosine moieties such as m 2 7,2'O G[5 ]ppp[5 ]m 2'O G and 2 -OH modifications on both m 7 guanosine moieties such as m 2 7,2'O G[5 ]ppp[5 ] m 2 7,2'O G are reported. Structures were confirmed by 1 H and 31 P NMR and mass spectral data.

Synthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki–Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors

“…As key precursors for functionalizing the C8-position by aqueous Suzuki–Miyaura cross-coupling reactions, 8-bromoguanosine 5′-monophosphate ( 8Br GMP, 11 , Supporting Information (SI)) and 8-bromo-2′- O -methylguanosine 5′-monophosphate ( 8Br m 2 ′ O GMP, 12 , SI) were prepared from either commercially available guanosine 5′-monophosphate (GMP, 9, SI) followed by conversion to triethylammonium salt or the m 2 ′ O GMP ( 10, SI) derivative obtained by the Yoshikawa procedure. , Subsequent treatment of 9 with saturated bromine water in sodium acetate buffer (pH 4.0) afforded the product in 62% yield after ion-exchange chromatography. This derivative required repeated purification steps to remove sodium acetate contamination.…”

“…Triethylammonium salts of m 7 GMP, m 7 GDP, GDP-Im, and m 7 GDP-Im were obtained as described in the literature . m 2 ′ O GMP was prepared according to the literature. , Sodium salts of the nucleotides were converted into triethylammonium salts using a Dowex 50WX8 ion-exchange resin.…”

“… 31 m 2 ′ O GMP was prepared according to the literature. 30 , 31 Sodium salts of the nucleotides were converted into triethylammonium salts using a Dowex 50WX8 ion-exchange resin.…”

Trinucleotide Cap Analogue Bearing a Locked Nucleic Acid Moiety: Synthesis, mRNA Modification, and Translation for Therapeutic Applications

“…We envisioned that the design of a new trinucleotide cap analogue containing an LNA moiety could serve as a potential molecular biology tool in the area of mRNA-based vaccines and mRNA transfection applications such as gene therapy, anticancer immunization, and protein production. Our continuous interest in the area of mRNA cap analogues for molecular biology applications − stimulated us to synthesize a trinucleotide cap analogue containing an LNA moiety and perform its biological evaluation. Herein we present the first report of the synthesis of a new trinucleotide cap analogue bearing an LNA moiety such as m 7(LNA) G­(5′)­ppp­(5′)­A m pG and its biological evaluation.…”