title: Phosphodiester cleavage of guanylyl-(3',3')-(2'-amino-2'-deoxyuridine): rate acceleration by the 2'-amino function.
abstract: Hydrolytic reactions of the structural analogue of guanylyl-(3',3')-uridine, guanylyl-(3',3')-(2'-amino-2'-deoxyuridine), having one of the 2'-hydroxyl groups replaced with an amino function, have been followed by RP HPLC in the pH range 0-13 at 90 degrees C. The results are compared to those obtained earlier with guanylyl-(3',3')-uridine, guanylyl-(3',3')-(2',5'-di-O-methyluridine), and uridylyl-(3',5')-uridine. Under basic conditions (pH > 8), the hydroxide ion-catalyzed cleavage of the P-O3' bond (first-order in [OH(-)]) yields a mixture of 2'-amino-2'-deoxyuridine and guanosine 2',3'-cyclic phosphate which is hydrolyzed to guanosine 2'- and 3'-phosphates. Under these conditions, guanylyl-(3',3')-(2'-amino-2'-deoxyuridine) is 10 times less reactive than guanylyl-(3',3')-uridine. Under acidic and neutral conditions (pH 3-8), where the pH-rate profile for the cleavage consists of two pH-independent regions (from pH 3 to pH 4 and from 6 to 8), guanylyl-(3',3')-(2'-amino-2'-deoxyuridine) is considerably reactive. For example, in the latter pH range, guanylyl-(3',3')-(2'-amino-2'-deoxyuridine) is more than 2 orders of magnitude more labile than guanylyl-(3',3')-(2',5'-di-O-methyluridine), while in the former pH range the reactivity difference is 1 order of magnitude. Under very acidic conditions (pH < 3), the isomerization giving guanylyl-(2',3')-(2'-amino-2'-deoxyuridine) and depurination yielding guanine (both first-order in [H(+)]) compete with the cleavage. The Zn(2+)-promoted cleavage ([Zn(2+)] = 5 mmol L(-)(1)) is 15 times faster than the uncatalyzed reaction at pH 5.6. The mechanisms of the reactions of guanylyl-(3',3')-(2'-amino-2'-deoxyuridine) are discussed, particularly focusing on the possible stabilization of phosphorane intermediate and/or transition state via an intramolecular hydrogen bonding by the 2'-amino group.
authors.affiliation: Department of Chemistry, University of Turku, FIN-20014 Turku, Finland. mikora@utu.fi
authors.forename: Mikko
authors.initials: M
authors.lastname: Ora
authors.forename: Heidi
authors.initials: H
authors.lastname: Linjalahti
authors.forename: Harri
authors.initials: H
authors.lastname: Lönnberg
mesh_terms: D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: C498153:guanylyl-(3',3')-(2'-amino-2'-deoxyuridine); D006147:Guanine; D015032:Zinc; D003857:Deoxyuridine