Conformational characteristics of rigid cyclic nucleotides. II. The solution conformation of. cap alpha. -nucleoside 3',5'-cyclic monophosphates and the role of the 2'-hydroxyl group
The first detailed study has been made of the 220-MHz NMR spectra of ..cap alpha..-adenosine 3',5'-cyclic monophosphate (I,..cap alpha..-cAMP), ..cap alpha..-uridine 3',5'-cyclic monophosphate (II, ..cap alpha..-cUMP), ..cap alpha..-cytidine 3',5'-cyclic monophosphate (III, ..cap alpha..-cCMP), ..cap alpha..-deoxyadenosine 3',5'-cyclic monophosphate (IV, ..cap alpha..-cdAMP), ..cap alpha..-5,6-dihydrouridine 3',5'-cyclic monophosphate (V, ..cap alpha..-cDHUMP), and ..beta..-5,6-dihydrouridine 3',5'-cyclic monophosphate (VI, ..beta..-cDHUMP) in D/sub 2/O solution. Analyses of the spectra of I-III were aided by the use of europium chloride as a shift reagent. A conformational analysis showed the sugar moieties of I-III to exhibit a conformation in the range /sub 2/T/sup 3/ to /sup 3/T/sub 2/ with an unusually high distortion from planarity, in contrast to the ..beta.. anomers which prefer /sup 3/E to /sub 4/T/sup 3/ and the acyclic mononucleotides which show a /sup 2/E reversible /sup 3/E equilibrium. This change in the preferred conformation is attributed to a repulsive interaction between the 2'-hydroxyl and the base. Removal of the 2'-hydroxyl group eliminates this interaction and causes a relaxation to a less strained system. This is clearly demonstrated in the sugar ring conformation of IV which exhibits a /sup 3/E to /sub 4/E pucker and a puckering amplitude that is less than in the ribo series. Hydrogenation of the pyrimidine ring of II and ..beta..-cUMP gave the 5,6-dihydro products V and VI. VI exhibits preference for a /sup 3/E to /sub 4/T/sup 3/ ribose ring conformation and in the case of V the 2'-hydroxyl-base interaction is markedly reduced owing to the increased flexibility of the aglycon. This results in a relaxation of the sugar ring conformation from the /sub 2/T/sup 3/ to /sup 3/T/sub 2/ in I-III back toward the /sup 3/E to /sub 4/T/sup 3/ conformation found in the ..beta.. anomers. Saturation of the base is not as effective as removal of the 2'-hydroxyl group in relieving the strain in these rigid systems. The phosphate ring is found to be in a flattened chair form in all cases.
- Research Organization:
- Argonne National Lab., IL
- OSTI ID:
- 5183493
- Journal Information:
- J. Am. Chem. Soc.; (United States), Vol. 99:23
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
NUCLEOTIDES
MOLECULAR STRUCTURE
CHEMICAL SHIFT
NUCLEAR MAGNETIC RESONANCE
PHOSPHATES
MAGNETIC RESONANCE
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS COMPOUNDS
RESONANCE
400301* - Organic Chemistry- Chemical & Physicochemical Properties- (-1987)