Document Detail


Hydrolytic reactions of guanosyl-(3',3')-uridine and guanosyl-(3',3')-(2',5'-di-O-methyluridine).
MedLine Citation:
PMID:  15339190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hydrolytic reactions of guanosyl-(3',3')-uridine and guanosyl-(3',3')-(2',5'-di-O-methyluridine) have been followed by RP HPLC over a wide pH range at 363.2 K in order to elucidate the role of the 2'-hydroxyl group as a hydrogen-bond donor upon departure of the 3'-uridine moiety. Under neutral and basic conditions, guanosyl-(3',3')-uridine undergoes hydroxide ion-catalyzed cleavage (first order in [OH(-)]) of the P-O3' bonds, giving uridine and guanosine 2',3'-cyclic monophosphates, which are subsequently hydrolyzed to a mixture of 2'- and 3'-monophosphates. This bond rupture is 23 times as fast as the corresponding cleavage of the P-O3' bond of guanosyl-(3',3')-(2',5'-di-O-methyluridine) to yield 2',5'-O-dimethyluridine and guanosine 2',3'-cyclic phosphate. Under acidic conditions, where the reactivity differences are smaller, depurination and isomerization compete with the cleavage. The effect of Zn(2+) on the cleavage of the P-O3' bonds of guanosyl-(3',3')-uridine is modest: about 6-fold acceleration was observed at [Zn(2+)] = 5 mmol L(-)(1) and pH 5.6. With guanosyl-(3',3')-(2',5'-di-O-methyluridine) the rate-acceleration effect is greater: a 37-fold acceleration was observed. The mechanisms of the partial reactions, in particular the effects of the 2'-hydroxyl group on the departure of the 3'-linked nucleoside, are discussed.
Authors:
Anu Kiviniemi; Tuomas Lönnberg; Mikko Ora
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  126     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-01     Completed Date:  2004-11-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11040-5     Citation Subset:  IM    
Affiliation:
Contribution from the Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
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MeSH Terms
Descriptor/Qualifier:
Guanosine / analogs & derivatives*,  chemistry
Hydrogen Bonding
Hydrogen-Ion Concentration
Hydrolysis
Kinetics
Phosphoric Acid Esters / chemistry
Uridine / analogs & derivatives*,  chemistry
Zinc / chemistry
Chemical
Reg. No./Substance:
0/Phosphoric Acid Esters; 118-00-3/Guanosine; 58-96-8/Uridine; 7440-66-6/Zinc

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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