Macrocyclic amines as catalysts of the hydrolysis of the triphosphate bridge of the mRNA 5'-cap structure.
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.
University of Turku, Department of Chemistry, FIN-20014 Turku, Finland.
Zhibo
Z
Zhang
Harri
H
Lönnberg
Satu
S
Mikkola
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D011122:Polyphosphates / Q000737:chemistry*; D012315:RNA Caps / Q000737:chemistry*
D000588:Amines; D006571:Heterocyclic Compounds; D011122:Polyphosphates; D012315:RNA Caps; C005692:triphosphoric acid