A1 Refereed original research article in a scientific journal
Phosphodiester cleavage of guanylyl-(3 ',3 ')-(2 '-amino-2 '-deoxyuridine): Rate acceleration by the 2 '-amino function
Authors: Ora M, Linjalahti H, Lonnberg H
Publisher: AMER CHEMICAL SOC
Publication year: 2005
Journal:: Journal of the American Chemical Society
Journal name in source: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Journal acronym: J AM CHEM SOC
Volume: 127
Issue: 6
First page : 1826
Last page: 1832
Number of pages: 7
ISSN: 0002-7863
DOI: https://doi.org/10.1021/ja045060+
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 RIP HPLC in the pH range 0-13 at 90degreesC. 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 T-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 Zn2+-promoted cleavage ([Zn2+] = 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.
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 RIP HPLC in the pH range 0-13 at 90degreesC. 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 T-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 Zn2+-promoted cleavage ([Zn2+] = 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.
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