Macrocyclic amines as catalysts of the hydrolysis of the triphosphate bridge of the mRNA 5′-cap structure

Abstract

The reactions of a 5′-cap model compound P¹-(7-methylguanosine) P³-guanosine 5′,5′-triphosphate, m⁷GpppG, were studied in the presence of three different macrocyclic amines (2–4) under neutral conditions. The only products observed in the absence of the macrocycles resulted from the base-catalysed imidazole ring-opening and the acid-catalysed cleavage of the N⁷-methylguanosine base, whereas in the presence of these catalysts hydrolysis of the triphosphate bridge predominated. The latter reaction yielded guanosine 5′-monophosphate, guanosine 5′-diphosphate, 7-methylguanosine 5′-monophosphate and 7-methylguanosine 5′-diphosphate as the initial products, indicating that both of the phosphoric anhydride bonds were cleaved. The overall catalytic activity of all three macrocycles was comparable. The hydrolysis to guanosine 5′-diphosphate and 7-methylguanosine 5′-monophosphate was slightly more favoured than the cleavage to yield guanosine 5′-monophosphate and 7-methylguanosine diphosphate. All the macrocycles also enhanced the subsequent hydrolysis of the nucleoside diphosphates, 2 being more efficient than 3 and 4.